1932

Abstract

Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and the ensuing production of type I interferon and other soluble mediators, which orchestrate innate and adaptive responses. We review several aspects of pDC biology that have recently come to the fore. We discuss emerging questions regarding the lineage affiliation and origin of pDCs and argue that these cells constitute an integral part of the dendritic cell lineage. We emphasize the specific function of pDCs as innate sentinels of virus infection, particularly their recognition of and distinct response to virus-infected cells. This essential evolutionary role of pDCs has been particularly important for the control of coronaviruses, as demonstrated by the recent COVID-19 pandemic. Finally, we highlight the key contribution of pDCs to systemic lupus erythematosus, in which therapeutic targeting of pDCs is currently underway.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-090122-041105
2024-06-28
2024-12-13
Loading full text...

Full text loading...

/deliver/fulltext/immunol/42/1/annurev-immunol-090122-041105.html?itemId=/content/journals/10.1146/annurev-immunol-090122-041105&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, et al. 1999.. The nature of the principal type 1 interferon–producing cells in human blood. . Science 284::183537
    [Crossref] [Google Scholar]
  2. 2.
    Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, et al. 1999.. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. . Nat. Med. 5::91923
    [Crossref] [Google Scholar]
  3. 3.
    Zhou Q, Zhao C, Yang Z, Qu R, Li Y, et al. 2023.. Cross-organ single-cell transcriptome profiling reveals macrophage and dendritic cell heterogeneity in zebrafish. . Cell Rep. 42::112793
    [Crossref] [Google Scholar]
  4. 4.
    Asselin-Paturel C, Trinchieri G. 2005.. Production of type I interferons: plasmacytoid dendritic cells and beyond. . J. Exp. Med. 202::46165
    [Crossref] [Google Scholar]
  5. 5.
    Liu YJ. 2005.. IPC: professional type 1 interferon–producing cells and plasmacytoid dendritic cell precursors. . Annu. Rev. Immunol. 23::275306
    [Crossref] [Google Scholar]
  6. 6.
    Swiecki M, Colonna M. 2015.. The multifaceted biology of plasmacytoid dendritic cells. . Nat. Rev. Immunol. 15::47185
    [Crossref] [Google Scholar]
  7. 7.
    Arroyo Hornero R, Idoyaga J. 2023.. Plasmacytoid dendritic cells: a dendritic cell in disguise. . Mol. Immunol. 159::3845
    [Crossref] [Google Scholar]
  8. 8.
    Musumeci A, Lutz K, Winheim E, Krug AB. 2019.. What makes a pDC: recent advances in understanding plasmacytoid DC development and heterogeneity. . Front. Immunol. 10::1222
    [Crossref] [Google Scholar]
  9. 9.
    Nutt SL, Chopin M. 2020.. Transcriptional networks driving dendritic cell differentiation and function. . Immunity 52::94256
    [Crossref] [Google Scholar]
  10. 10.
    Gilliet M, Cao W, Liu YJ. 2008.. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. . Nat. Rev. Immunol. 8::594606
    [Crossref] [Google Scholar]
  11. 11.
    Webster B, Assil S, Dreux M. 2016.. Cell-cell sensing of viral infection by plasmacytoid dendritic cells. . J. Virol. 90::1005053
    [Crossref] [Google Scholar]
  12. 12.
    Barrat FJ, Su L. 2019.. A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection. . J. Exp. Med. 216::197485
    [Crossref] [Google Scholar]
  13. 13.
    Greene TT, Zuniga EI. 2021.. Type I interferon induction and exhaustion during viral infection: plasmacytoid dendritic cells and emerging COVID-19 findings. . Viruses 13::1839
    [Crossref] [Google Scholar]
  14. 14.
    Ganguly D. 2022.. Plasmacytoid Dendritic Cells. Berlin:: Springer
    [Google Scholar]
  15. 15.
    Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V. 2011.. Plasmacytoid dendritic cells: recent progress and open questions. . Annu. Rev. Immunol. 29::16383
    [Crossref] [Google Scholar]
  16. 16.
    Reizis B. 2019.. Plasmacytoid dendritic cells: development, regulation, and function. . Immunity 50::3750
    [Crossref] [Google Scholar]
  17. 17.
    Cabeza-Cabrerizo M, Cardoso A, Minutti CM, Pereira da Costa M, Reis e Sousa C. 2021.. Dendritic cells revisited. . Annu. Rev. Immunol. 39::13166
    [Crossref] [Google Scholar]
  18. 18.
    Ziegler-Heitbrock L, Ohteki T, Ginhoux F, Shortman K, Spits H. 2023.. Reclassifying plasmacytoid dendritic cells as innate lymphocytes. . Nat. Rev. Immunol. 23::12
    [Crossref] [Google Scholar]
  19. 19.
    Reizis B, Idoyaga J, Dalod M, Barrat F, Naik S, et al. 2023.. Reclassification of plasmacytoid dendritic cells as innate lymphocytes is premature. . Nat. Rev. Immunol. 23::33637
    [Crossref] [Google Scholar]
  20. 20.
    Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, et al. 2014.. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. . Nat. Rev. Immunol. 14::57178
    [Crossref] [Google Scholar]
  21. 21.
    Liu K, Waskow C, Liu X, Yao K, Hoh J, Nussenzweig M. 2007.. Origin of dendritic cells in peripheral lymphoid organs of mice. . Nat. Immunol. 8::57883
    [Crossref] [Google Scholar]
  22. 22.
    Zhan Y, Chow KV, Soo P, Xu Z, Brady JL, et al. 2016.. Plasmacytoid dendritic cells are short-lived: reappraising the influence of migration, genetic factors and activation on estimation of lifespan. . Sci. Rep. 6::25060
    [Crossref] [Google Scholar]
  23. 23.
    Upadhaya S, Sawai CM, Papalexi E, Rashidfarrokhi A, Jang G, et al. 2018.. Kinetics of adult hematopoietic stem cell differentiation in vivo. . J. Exp. Med. 215::281532
    [Crossref] [Google Scholar]
  24. 24.
    Jang G, Contreras Castillo S, Esteva E, Upadhaya S, Feng J, et al. 2023.. Stem cell decoupling underlies impaired lymphoid development during aging. . PNAS 120::e2302019120
    [Crossref] [Google Scholar]
  25. 25.
    Fogg DK, Sibon C, Miled C, Jung S, Aucouturier P, et al. 2006.. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. . Science 311::8387
    [Crossref] [Google Scholar]
  26. 26.
    Feng J, Pucella JN, Jang G, Alcantara-Hernandez M, Upadhaya S, et al. 2022.. Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells. . Immunity 55::40522.e11
    [Crossref] [Google Scholar]
  27. 27.
    D'Amico A, Wu L. 2003.. The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. . J. Exp. Med. 198::293303
    [Crossref] [Google Scholar]
  28. 28.
    Karsunky H, Merad M, Cozzio A, Weissman IL, Manz MG. 2003.. Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. . J. Exp. Med. 198::30513
    [Crossref] [Google Scholar]
  29. 29.
    Waskow C, Liu K, Darrasse-Jeze G, Guermonprez P, Ginhoux F, et al. 2008.. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. . Nat. Immunol. 9::67683
    [Crossref] [Google Scholar]
  30. 30.
    Gilliet M, Boonstra A, Paturel C, Antonenko S, Xu XL, et al. 2002.. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. . J. Exp. Med. 195::95358
    [Crossref] [Google Scholar]
  31. 31.
    Naik SH, Proietto AI, Wilson NS, Dakic A, Schnorrer P, et al. 2005.. Cutting edge: generation of splenic CD8+ and CD8 dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures. . J. Immunol. 174::659297
    [Crossref] [Google Scholar]
  32. 32.
    Tiniakou I, Hsu P-F, Lopez-Zepeda LS, Garipler G, Esteva E, et al. 2024.. Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation. . Sci. Immunol. In press
    [Google Scholar]
  33. 33.
    Wang Y, Huang G, Zeng H, Yang K, Lamb RF, Chi H. 2013.. Tuberous sclerosis 1 (Tsc1)-dependent metabolic checkpoint controls development of dendritic cells. . PNAS 110::E4894903
    [Google Scholar]
  34. 34.
    Shigematsu H, Reizis B, Iwasaki H, Mizuno S, Hu D, et al. 2004.. Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin. . Immunity 21::4353
    [Crossref] [Google Scholar]
  35. 35.
    Onai N, Kurabayashi K, Hosoi-Amaike M, Toyama-Sorimachi N, Matsushima K, et al. 2013.. A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential. . Immunity 38::94357
    [Crossref] [Google Scholar]
  36. 36.
    Rodrigues PF, Alberti-Servera L, Eremin A, Grajales-Reyes GE, Ivanek R, Tussiwand R. 2018.. Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells. . Nat. Immunol. 19::71122
    [Crossref] [Google Scholar]
  37. 37.
    Dress RJ, Dutertre CA, Giladi A, Schlitzer A, Low I, et al. 2019.. Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage. . Nat. Immunol. 20::85264
    [Crossref] [Google Scholar]
  38. 38.
    Pelayo R, Hirose J, Huang J, Garrett KP, Delogu A, et al. 2005.. Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow. . Blood 105::440715
    [Crossref] [Google Scholar]
  39. 39.
    Sathe P, Vremec D, Wu L, Corcoran L, Shortman K. 2013.. Convergent differentiation: myeloid and lymphoid pathways to murine plasmacytoid dendritic cells. . Blood 121::1119
    [Crossref] [Google Scholar]
  40. 40.
    Corcoran L, Ferrero I, Vremec D, Lucas K, Waithman J, et al. 2003.. The lymphoid past of mouse plasmacytoid cells and thymic dendritic cells. . J. Immunol. 170::492632
    [Crossref] [Google Scholar]
  41. 41.
    Herman JS, Sagar Grun D. 2018.. FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data. . Nat. Methods 15::37986
    [Crossref] [Google Scholar]
  42. 42.
    Reizis B. 2010.. Regulation of plasmacytoid dendritic cell development. . Curr. Opin. Immunol. 22::20611
    [Crossref] [Google Scholar]
  43. 43.
    Durai V, Bagadia P, Granja JM, Satpathy AT, Kulkarni DH, et al. 2019.. Cryptic activation of an Irf8 enhancer governs cDC1 fate specification. . Nat. Immunol. 20::116173
    [Crossref] [Google Scholar]
  44. 44.
    Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, et al. 2008.. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. . Cell 135::3748
    [Crossref] [Google Scholar]
  45. 45.
    Cao W, Zhang L, Rosen DB, Bover L, Watanabe G, et al. 2007.. BDCA2/FcεRIγ complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. . PLOS Biol. 5::e248
    [Crossref] [Google Scholar]
  46. 46.
    Vogt TK, Link A, Perrin J, Finke D, Luther SA. 2009.. Novel function for interleukin-7 in dendritic cell development. . Blood 113::396168
    [Crossref] [Google Scholar]
  47. 47.
    Blasius AL, Barchet W, Cella M, Colonna M. 2007.. Development and function of murine B220+CD11c+NK1.1+ cells identify them as a subset of NK cells. . J. Exp. Med. 204::256168
    [Crossref] [Google Scholar]
  48. 48.
    Caminschi I, Ahmet F, Heger K, Brady J, Nutt SL, et al. 2007.. Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells. . J. Exp. Med. 204::257990
    [Crossref] [Google Scholar]
  49. 49.
    Vosshenrich CA, Lesjean-Pottier S, Hasan M, Richard–Le Goff O, Corcuff E, et al. 2007.. CD11cloB220+ interferon-producing killer dendritic cells are activated natural killer cells. . J. Exp. Med. 204::256978
    [Crossref] [Google Scholar]
  50. 50.
    Harman BC, Miller JP, Nikbakht N, Gerstein R, Allman D. 2006.. Mouse plasmacytoid dendritic cells derive exclusively from estrogen-resistant myeloid progenitors. . Blood 108::87885
    [Crossref] [Google Scholar]
  51. 51.
    Bar-On L, Birnberg T, Lewis KL, Edelson BT, Bruder D, et al. 2010.. CX3CR1+CD8α+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells. . PNAS 107::1474550
    [Crossref] [Google Scholar]
  52. 52.
    Villani AC, Satija R, Reynolds G, Sarkizova S, Shekhar K, et al. 2017.. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. . Science 356::eaah4573
    [Crossref] [Google Scholar]
  53. 53.
    See P, Dutertre CA, Chen J, Gunther P, McGovern N, et al. 2017.. Mapping the human DC lineage through the integration of high-dimensional techniques. . Science 356::eaag3009
    [Crossref] [Google Scholar]
  54. 54.
    Alcantara-Hernandez M, Leylek R, Wagar LE, Engleman EG, Keler T, et al. 2017.. High-dimensional phenotypic mapping of human dendritic cells reveals interindividual variation and tissue specialization. . Immunity 47::103750.e6
    [Crossref] [Google Scholar]
  55. 55.
    Zhang H, Gregorio JD, Iwahori T, Zhang X, Choi O, et al. 2017.. A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes. . PNAS 114::198893
    [Crossref] [Google Scholar]
  56. 56.
    Leylek R, Alcantara-Hernandez M, Lanzar Z, Ludtke A, Perez OA, et al. 2019.. Integrated cross-species analysis identifies a conserved transitional dendritic cell population. . Cell Rep. 29::373650.e8
    [Crossref] [Google Scholar]
  57. 57.
    Valente M, Collinet N, Vu Manh TP, Popoff D, Rahmani K, et al. 2023.. Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells. . Nat. Immunol. 24::71428
    [Crossref] [Google Scholar]
  58. 58.
    Rodrigues PF, Kouklas A, Cvijetic G, Bouladoux N, Mitrovic M, et al. 2023. pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells. . Sci. Immunol. 8::eadd4132
    [Crossref] [Google Scholar]
  59. 59.
    Sulczewski FB, Maqueda-Alfaro RA, Alcantara-Hernandez M, Perez OA, Saravanan S, et al. 2023.. Transitional dendritic cells are distinct from conventional DC2 precursors and mediate proinflammatory antiviral responses. . Nat. Immunol. 24::126580
    [Crossref] [Google Scholar]
  60. 60.
    Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. 2010.. Development of monocytes, macrophages, and dendritic cells. . Science 327::65661
    [Crossref] [Google Scholar]
  61. 61.
    Schraml BU, van Blijswijk J, Zelenay S, Whitney PG, Filby A, et al. 2013.. Genetic tracing via DNGR-1 expression history defines dendritic cells as a hematopoietic lineage. . Cell 154::84358
    [Crossref] [Google Scholar]
  62. 62.
    Liu TT, Kim S, Desai P, Kim DH, Huang X, et al. 2022.. Ablation of cDC2 development by triple mutations within the Zeb2 enhancer. . Nature 607::14248
    [Crossref] [Google Scholar]
  63. 63.
    Bagadia P, Huang X, Liu TT, Durai V, Grajales-Reyes GE, et al. 2019.. An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development. . Nat. Immunol. 20::117485
    [Crossref] [Google Scholar]
  64. 64.
    Lutz K, Musumeci A, Sie C, Dursun E, Winheim E, et al. 2022.. Ly6D+Siglec-H+ precursors contribute to conventional dendritic cells via a Zbtb46+Ly6D+ intermediary stage. . Nat. Commun. 13::3456
    [Crossref] [Google Scholar]
  65. 65.
    Vollstedt S, O'Keeffe M, Odermatt B, Beat R, Glanzmann B, et al. 2004.. Treatment of neonatal mice with Flt3 ligand leads to changes in dendritic cell subpopulations associated with enhanced IL-12 and IFN-α production. . Eur. J. Immunol. 34::184960
    [Crossref] [Google Scholar]
  66. 66.
    Tussiwand R, Onai N, Mazzucchelli L, Manz MG. 2005.. Inhibition of natural type I IFN–producing and dendritic cell development by a small molecule receptor tyrosine kinase inhibitor with Flt3 affinity. . J. Immunol. 175::367480
    [Crossref] [Google Scholar]
  67. 67.
    Ginhoux F, Liu K, Helft J, Bogunovic M, Greter M, et al. 2009.. The origin and development of nonlymphoid tissue CD103+ DCs. . J. Exp. Med. 206::311530
    [Crossref] [Google Scholar]
  68. 68.
    Sathaliyawala T, O'Gorman WE, Greter M, Bogunovic M, Konjufca V, et al. 2010.. Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. . Immunity 33::597606
    [Crossref] [Google Scholar]
  69. 69.
    Lau CM, Nish SA, Yogev N, Waisman A, Reiner SL, Reizis B. 2016.. Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses. . J. Exp. Med. 213::41531
    [Crossref] [Google Scholar]
  70. 70.
    Sichien D, Scott CL, Martens L, Vanderkerken M, Van Gassen S, et al. 2016.. IRF8 transcription factor controls survival and function of terminally differentiated conventional and plasmacytoid dendritic cells, respectively. . Immunity 45::62640
    [Crossref] [Google Scholar]
  71. 71.
    Murakami K, Sasaki H, Nishiyama A, Kurotaki D, Kawase W, et al. 2021.. A RUNX-CBFβ-driven enhancer directs the Irf8 dose–dependent lineage choice between DCs and monocytes. . Nat. Immunol. 22::30111
    [Crossref] [Google Scholar]
  72. 72.
    Xu H, Li Z, Kuo CC, Gotz K, Look T, et al. 2023.. A lncRNA identifies Irf8 enhancer element in negative feedback control of dendritic cell differentiation. . eLife 12::e83342
    [Crossref] [Google Scholar]
  73. 73.
    Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, et al. 2005.. TLR11 activation of dendritic cells by a protozoan profilin-like protein. . Science 308::162629
    [Crossref] [Google Scholar]
  74. 74.
    McCartney S, Vermi W, Gilfillan S, Cella M, Murphy TL, et al. 2009.. Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells. . J. Exp. Med. 206::296776
    [Crossref] [Google Scholar]
  75. 75.
    Lauterbach H, Bathke B, Gilles S, Traidl-Hoffmann C, Luber CA, et al. 2010.. Mouse CD8α+ DCs and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC. . J. Exp. Med. 207::270317
    [Crossref] [Google Scholar]
  76. 76.
    Tel J, Schreibelt G, Sittig SP, Mathan TS, Buschow SI, et al. 2013.. Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets. . Blood 121::45967
    [Crossref] [Google Scholar]
  77. 77.
    Di Pucchio T, Chatterjee B, Smed-Sorensen A, Clayton S, Palazzo A, et al. 2008.. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. . Nat. Immunol. 9::55157
    [Crossref] [Google Scholar]
  78. 78.
    Oberkampf M, Guillerey C, Mouries J, Rosenbaum P, Fayolle C, et al. 2018.. Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells. . Nat. Commun. 9::2241
    [Crossref] [Google Scholar]
  79. 79.
    Grajkowska LT, Ceribelli M, Lau CM, Warren ME, Tiniakou I, et al. 2017.. Isoform-specific expression and feedback regulation of E protein TCF4 control dendritic cell lineage specification. . Immunity 46::6577
    [Crossref] [Google Scholar]
  80. 80.
    Ghosh HS, Ceribelli M, Matos I, Lazarovici A, Bussemaker HJ, et al. 2014.. ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2. . J. Exp. Med. 211::162335
    [Crossref] [Google Scholar]
  81. 81.
    Wu X, Briseno CG, Grajales-Reyes GE, Haldar M, Iwata A, et al. 2016.. Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate. . PNAS 113::1477580
    [Crossref] [Google Scholar]
  82. 82.
    Scott CL, Soen B, Martens L, Skrypek N, Saelens W, et al. 2016.. The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. . J. Exp. Med. 213::897911
    [Crossref] [Google Scholar]
  83. 83.
    Hacker C, Kirsch RD, Ju XS, Hieronymus T, Gust TC, et al. 2003.. Transcriptional profiling identifies Id2 function in dendritic cell development. . Nat. Immunol. 4::38086
    [Crossref] [Google Scholar]
  84. 84.
    Weigert A, Weichand B, Sekar D, Sha W, Hahn C, et al. 2012.. HIF-1alpha is a negative regulator of plasmacytoid DC development in vitro and in vivo. . Blood 120::30016
    [Crossref] [Google Scholar]
  85. 85.
    Singh Rawat B, Venkataraman R, Budhwar R, Tailor P. 2022.. Methionine- and choline-deficient diet identifies an essential role for DNA methylation in plasmacytoid dendritic cell biology. . J. Immunol. 208::88197
    [Crossref] [Google Scholar]
  86. 86.
    Czeh M, Stable S, Kramer S, Tepe L, Talyan S, et al. 2022.. DNMT1 deficiency impacts on plasmacytoid dendritic cells in homeostasis and autoimmune disease. . J. Immunol. 208::35870
    [Crossref] [Google Scholar]
  87. 87.
    Ghosh HS, Cisse B, Bunin A, Lewis KL, Reizis B. 2010.. Continuous expression of the transcription factor E2-2 maintains the cell fate of mature plasmacytoid dendritic cells. . Immunity 33::90516
    [Crossref] [Google Scholar]
  88. 88.
    Manh TP, Alexandre Y, Baranek T, Crozat K, Dalod M. 2013.. Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation. . Eur. J. Immunol. 43::170615
    [Crossref] [Google Scholar]
  89. 89.
    Abbas A, Vu Manh TP, Valente M, Collinet N, Attaf N, et al. 2020.. The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection. . Nat. Immunol. 21::98397
    [Crossref] [Google Scholar]
  90. 90.
    O'Keeffe M, Hochrein H, Vremec D, Caminschi I, Miller JL, et al. 2002.. Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8+ dendritic cells only after microbial stimulus. . J. Exp. Med. 196::130719
    [Crossref] [Google Scholar]
  91. 91.
    Yun TJ, Igarashi S, Zhao H, Perez OA, Pereira MR, et al. 2021.. Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells. . Sci. Immunol. 6::eabc7302
    [Crossref] [Google Scholar]
  92. 92.
    Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ. 1997.. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. . J. Exp. Med. 185::110111
    [Crossref] [Google Scholar]
  93. 93.
    Cella M, Facchetti F, Lanzavecchia A, Colonna M. 2000.. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. . Nat. Immunol. 1::30510
    [Crossref] [Google Scholar]
  94. 94.
    Alculumbre SG, Saint-Andre V, Di Domizio J, Vargas P, Sirven P, et al. 2018.. Diversification of human plasmacytoid predendritic cells in response to a single stimulus. . Nat. Immunol. 19::6375
    [Crossref] [Google Scholar]
  95. 95.
    Ghanem MH, Shih AJ, Khalili H, Werth EG, Chakrabarty JK, et al. 2022.. Proteomic and single-cell transcriptomic dissection of human plasmacytoid dendritic cell response to influenza virus. . Front. Immunol. 13::814627
    [Crossref] [Google Scholar]
  96. 96.
    Facchetti F, Cigognetti M, Fisogni S, Rossi G, Lonardi S, Vermi W. 2016.. Neoplasms derived from plasmacytoid dendritic cells. . Mod. Pathol. 29::98111
    [Crossref] [Google Scholar]
  97. 97.
    Chaperot L, Bendriss N, Manches O, Gressin R, Maynadie M, et al. 2001.. Identification of a leukemic counterpart of the plasmacytoid dendritic cells. . Blood 97::321017
    [Crossref] [Google Scholar]
  98. 98.
    Sapienza MR, Fuligni F, Agostinelli C, Tripodo C, Righi S, et al. 2014.. Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-κB pathway inhibition. . Leukemia 28::160616
    [Crossref] [Google Scholar]
  99. 99.
    Ceribelli M, Hou ZE, Kelly PN, Huang DW, Wright G, et al. 2016.. A druggable TCF4- and BRD4-dependent transcriptional network sustains malignancy in blastic plasmacytoid dendritic cell neoplasm. . Cancer Cell 30::76478
    [Crossref] [Google Scholar]
  100. 100.
    Luskin MR, Lane AA. 2024.. Tagraxofusp for blastic plasmacytoid dendritic cell neoplasm. . Haematologica 109::4452
    [Google Scholar]
  101. 101.
    Togami K, Chung SS, Madan V, Booth CAG, Kenyon CM, et al. 2022.. Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis. . Cancer Discov. 12::52241
    [Crossref] [Google Scholar]
  102. 102.
    Kubota S, Tokunaga K, Umezu T, Yokomizo-Nakano T, Sun Y, et al. 2019.. Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm. . Nat. Commun. 10::1653
    [Crossref] [Google Scholar]
  103. 103.
    Sawai CM, Sisirak V, Ghosh HS, Hou EZ, Ceribelli M, et al. 2013.. Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells. . J. Exp. Med. 210::215159
    [Crossref] [Google Scholar]
  104. 104.
    Luskin MR, Kim AS, Patel SS, Wright K, LeBoeuf NR, Lane AA. 2020.. Evidence for separate transformation to acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm from a shared ancestral hematopoietic clone. . Leuk. Lymphoma 61::225861
    [Crossref] [Google Scholar]
  105. 105.
    Xiao W, Chan A, Waarts MR, Mishra T, Liu Y, et al. 2021.. Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia. . Blood 137::137791
    [Crossref] [Google Scholar]
  106. 106.
    El Hussein S, Wang W. 2023.. Plasmacytoid dendritic cells in the setting of myeloid neoplasms: diagnostic guide to challenging pathologic presentations. . Br. J. Haematol. 200::54555
    [Crossref] [Google Scholar]
  107. 107.
    Griffin GK, Booth CA, Togami K, Chung SS, Ssozi D, et al. 2023.. Ultraviolet radiation shapes dendritic cell leukaemia transformation in the skin. . Nature 618::83441
    [Crossref] [Google Scholar]
  108. 108.
    Honda K, Yanai H, Negishi H, Asagiri M, Sato M, et al. 2005.. IRF-7 is the master regulator of type-I interferon-dependent immune responses. . Nature 434::77277
    [Crossref] [Google Scholar]
  109. 109.
    Barchet W, Cella M, Odermatt B, Asselin-Paturel C, Colonna M, Kalinke U. 2002.. Virus-induced interferon α production by a dendritic cell subset in the absence of feedback signaling in vivo. . J. Exp. Med. 195::50716
    [Crossref] [Google Scholar]
  110. 110.
    Kerkmann M, Rothenfusser S, Hornung V, Towarowski A, Wagner M, et al. 2003.. Activation with CpG-A and CpG-B oligonucleotides reveals two distinct regulatory pathways of type I IFN synthesis in human plasmacytoid dendritic cells. . J. Immunol. 170::446574
    [Crossref] [Google Scholar]
  111. 111.
    Tomasello E, Naciri K, Chelbi R, Bessou G, Fries A, et al. 2018.. Molecular dissection of plasmacytoid dendritic cell activation in vivo during a viral infection. . EMBO J. 37::e98836
    [Crossref] [Google Scholar]
  112. 112.
    Ito T, Kanzler H, Duramad O, Cao W, Liu YJ. 2006.. Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells. . Blood 107::242331
    [Crossref] [Google Scholar]
  113. 113.
    Marie I, Durbin JE, Levy DE. 1998.. Differential viral induction of distinct interferon-α genes by positive feedback through interferon regulatory factor 7. . EMBO J. 17::666069
    [Crossref] [Google Scholar]
  114. 114.
    Piehler J, Thomas C, Garcia KC, Schreiber G. 2012.. Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation. . Immunol. Rev. 250::31734
    [Crossref] [Google Scholar]
  115. 115.
    Guiducci C, Ott G, Chan JH, Damon E, Calacsan C, et al. 2006.. Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. . J. Exp. Med. 203::19992008
    [Crossref] [Google Scholar]
  116. 116.
    Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, et al. 2005.. Spatiotemporal regulation of MyD88–IRF-7 signalling for robust type-I interferon induction. . Nature 434::103540
    [Crossref] [Google Scholar]
  117. 117.
    Blasius AL, Arnold CN, Georgel P, Rutschmann S, Xia Y, et al. 2010.. Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells. . PNAS 107::1997378
    [Crossref] [Google Scholar]
  118. 118.
    Sasai M, Linehan MM, Iwasaki A. 2010.. Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. . Science 329::153034
    [Crossref] [Google Scholar]
  119. 119.
    Prandini A, Salvi V, Colombo F, Moratto D, Lorenzi L, et al. 2016.. Impairment of dendritic cell functions in patients with adaptor protein 3 complex deficiency. . Blood 127::338286
    [Crossref] [Google Scholar]
  120. 120.
    Cao W, Manicassamy S, Tang H, Kasturi SP, Pirani A, et al. 2008.. Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI3K-mTOR-p70S6K pathway. . Nat. Immunol. 9::115764
    [Crossref] [Google Scholar]
  121. 121.
    Guiducci C, Ghirelli C, Marloie-Provost MA, Matray T, Coffman RL, et al. 2008.. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation. . J. Exp. Med. 205::31522
    [Crossref] [Google Scholar]
  122. 122.
    Esashi E, Bao M, Wang YH, Cao W, Liu YJ. 2012.. PACSIN1 regulates the TLR7/9-mediated type I interferon response in plasmacytoid dendritic cells. . Eur. J. Immunol. 42::57379
    [Crossref] [Google Scholar]
  123. 123.
    Schmidt B, Ashlock BM, Foster H, Fujimura SH, Levy JA. 2005.. HIV-infected cells are major inducers of plasmacytoid dendritic cell interferon production, maturation, and migration. . Virology 343::25666
    [Crossref] [Google Scholar]
  124. 124.
    Takahashi K, Asabe S, Wieland S, Garaigorta U, Gastaminza P, et al. 2010.. Plasmacytoid dendritic cells sense hepatitis C virus–infected cells, produce interferon, and inhibit infection. . PNAS 107::743136
    [Crossref] [Google Scholar]
  125. 125.
    Dreux M, Garaigorta U, Boyd B, Decembre E, Chung J, et al. 2012.. Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity. . Cell Host Microbe 12::55870
    [Crossref] [Google Scholar]
  126. 126.
    Frenz T, Graalmann L, Detje CN, Doring M, Grabski E, et al. 2014.. Independent of plasmacytoid dendritic cell (pDC) infection, pDC triggered by virus-infected cells mount enhanced type I IFN responses of different composition as opposed to pDC stimulated with free virus. . J. Immunol. 193::2496503
    [Crossref] [Google Scholar]
  127. 127.
    Venet M, Ribeiro MS, Decembre E, Bellomo A, Joshi G, et al. 2023.. Severe COVID-19 patients have impaired plasmacytoid dendritic cell–mediated control of SARS-CoV-2. . Nat. Commun. 14::694
    [Crossref] [Google Scholar]
  128. 128.
    Onodi F, Bonnet-Madin L, Meertens L, Karpf L, Poirot J, et al. 2021.. SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4. . J. Exp. Med. 218::e20201387
    [Crossref] [Google Scholar]
  129. 129.
    Assil S, Coleon S, Dong C, Decembre E, Sherry L, et al. 2019.. Plasmacytoid dendritic cells and infected cells form an interferogenic synapse required for antiviral responses. . Cell Host Microbe 25::73045.e6
    [Crossref] [Google Scholar]
  130. 130.
    Garcia-Nicolas O, Auray G, Sautter CA, Rappe JC, McCullough KC, et al. 2016.. Sensing of porcine reproductive and respiratory syndrome virus–infected macrophages by plasmacytoid dendritic cells. . Front. Microbiol. 7::771
    [Crossref] [Google Scholar]
  131. 131.
    Saitoh SI, Abe F, Kanno A, Tanimura N, Mori Saitoh Y, et al. 2017.. TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells. . Nat. Commun. 8::1592
    [Crossref] [Google Scholar]
  132. 132.
    Garcia-Nicolas O, Godel A, Zimmer G, Summerfield A. 2023.. Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation. . Cell Mol. Immunol. 20::83549
    [Crossref] [Google Scholar]
  133. 133.
    Moore-Fried J, Paul M, Jing Z, Fooksman D, Lauvau G. 2022.. CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice. . eLife 11::e78873
    [Crossref] [Google Scholar]
  134. 134.
    Taniguchi T, Takaoka A. 2001.. A weak signal for strong responses: interferon-α/β revisited. . Nat. Rev. Mol. Cell Biol. 2::37886
    [Crossref] [Google Scholar]
  135. 135.
    Gough DJ, Messina NL, Clarke CJ, Johnstone RW, Levy DE. 2012.. Constitutive type I interferon modulates homeostatic balance through tonic signaling. . Immunity 36::16674
    [Crossref] [Google Scholar]
  136. 136.
    Kim S, Kaiser V, Beier E, Bechheim M, Guenthner-Biller M, et al. 2014.. Self-priming determines high type I IFN production by plasmacytoid dendritic cells. . Eur. J. Immunol. 44::80718
    [Crossref] [Google Scholar]
  137. 137.
    Schaupp L, Muth S, Rogell L, Kofoed-Branzk M, Melchior F, et al. 2020.. Microbiota-induced type I interferons instruct a poised basal state of dendritic cells. . Cell 181::108096.e19
    [Crossref] [Google Scholar]
  138. 138.
    Stefan KL, Kim MV, Iwasaki A, Kasper DL. 2020.. Commensal microbiota modulation of natural resistance to virus infection. . Cell 183::131224.e10
    [Crossref] [Google Scholar]
  139. 139.
    Geva-Zatorsky N, Sefik E, Kua L, Pasman L, Tan TG, et al. 2017.. Mining the human gut microbiota for immunomodulatory organisms. . Cell 168::92843.e11
    [Crossref] [Google Scholar]
  140. 140.
    Bunin A, Sisirak V, Ghosh HS, Grajkowska LT, Hou ZE, et al. 2015.. Protein tyrosine phosphatase PTPRS is an inhibitory receptor on human and murine plasmacytoid dendritic cells. . Immunity 43::27788
    [Crossref] [Google Scholar]
  141. 141.
    Di Domizio J, Belkhodja C, Chenuet P, Fries A, Murray T, et al. 2020.. The commensal skin microbiota triggers type I IFN–dependent innate repair responses in injured skin. . Nat. Immunol. 21::103445
    [Crossref] [Google Scholar]
  142. 142.
    Malireddi RKS, Sharma BR, Kanneganti T-D. 2024.. Innate immunity in protection and pathogenesis during coronavirus infections and COVID-19. . Annu. Rev. Immunol. 42::61545
    [Google Scholar]
  143. 143.
    Van der Sluis RM, Holm CK, Jakobsen MR. 2022.. Plasmacytoid dendritic cells during COVID-19: ally or adversary?. Cell Rep. 40::111148
    [Crossref] [Google Scholar]
  144. 144.
    Zhang Q, Bastard P, Effort CHG, Cobat A, Casanova JL. 2022.. Human genetic and immunological determinants of critical COVID-19 pneumonia. . Nature 603::58798
    [Crossref] [Google Scholar]
  145. 145.
    Cervantes-Barragan L, Zust R, Weber F, Spiegel M, Lang KS, et al. 2007.. Control of coronavirus infection through plasmacytoid-dendritic-cell-derived type I interferon. . Blood 109::113137
    [Crossref] [Google Scholar]
  146. 146.
    Cervantes-Barragan L, Kalinke U, Zust R, Konig M, Reizis B, et al. 2009.. Type I IFN–mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection. . J. Immunol. 182::1099106
    [Crossref] [Google Scholar]
  147. 147.
    Bocharov G, Zust R, Cervantes-Barragan L, Luzyanina T, Chiglintsev E, et al. 2010.. A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections. . PLOS Pathog. 6::e1001017
    [Crossref] [Google Scholar]
  148. 148.
    Cervantes-Barragan L, Lewis KL, Firner S, Thiel V, Hugues S, et al. 2012.. Plasmacytoid dendritic cells control T-cell response to chronic viral infection. . PNAS 109::301217
    [Crossref] [Google Scholar]
  149. 149.
    Scheuplein VA, Seifried J, Malczyk AH, Miller L, Hocker L, et al. 2015.. High secretion of interferons by human plasmacytoid dendritic cells upon recognition of Middle East respiratory syndrome coronavirus. . J. Virol. 89::385969
    [Crossref] [Google Scholar]
  150. 150.
    Robertson S, Bedard O, McNally K, Shaia C, Clancy C, et al. 2023.. Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19. . bioRxiv 2021.09.17.460664. https://doi.org/10.1101/2021.09.17.460664
  151. 151.
    Ghimire R, Shrestha R, Amaradhi R, Patton T, Whitley C, et al. 2023.. Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection. . bioRxiv 2023.05.08.539929. https://doi.org/2023.05.08.539929
  152. 152.
    Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, et al. 2020.. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. . Science 370::eabd4570
    [Crossref] [Google Scholar]
  153. 153.
    Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, et al. 2021.. X-linked recessive TLR7 deficiency in ∼1% of men under 60 years old with life-threatening COVID-19. . Sci. Immunol. 6::eabl4348
    [Crossref] [Google Scholar]
  154. 154.
    Cervantes-Barragan L, Vanderheiden A, Royer CJ, Davis-Gardner ME, Ralfs P, et al. 2021.. Plasmacytoid dendritic cells produce type I interferon and reduce viral replication in airway epithelial cells after SARS-CoV-2 infection. . bioRxiv 2021.05.12.443948. https://doi.org/2021.05.12.443948
  155. 155.
    Severa M, Diotti RA, Etna MP, Rizzo F, Fiore S, et al. 2021.. Differential plasmacytoid dendritic cell phenotype and type I interferon response in asymptomatic and severe COVID-19 infection. . PLOS Pathog. 17::e1009878
    [Crossref] [Google Scholar]
  156. 156.
    van der Sluis RM, Cham LB, Gris-Oliver A, Gammelgaard KR, Pedersen JG, et al. 2022.. TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS-CoV-2 infection. . EMBO J. 41::e109622
    [Crossref] [Google Scholar]
  157. 157.
    Laurent P, Yang C, Rendeiro AF, Nilsson-Payant BE, Carrau L, et al. 2022.. Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19. . Sci. Immunol. 7::eadd4906
    [Crossref] [Google Scholar]
  158. 158.
    Laing AG, Lorenc A, Del Molino Del Barrio I, Das A, Fish M, et al. 2020.. A dynamic COVID-19 immune signature includes associations with poor prognosis. . Nat. Med. 26::162335
    [Crossref] [Google Scholar]
  159. 159.
    Arunachalam PS, Wimmers F, Mok CKP, Perera RA, Scott M, et al. 2020.. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. . Science 369::121020
    [Crossref] [Google Scholar]
  160. 160.
    Zhou R, To KK, Wong YC, Liu L, Zhou B, et al. 2020.. Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses. . Immunity 53::86477.e5
    [Crossref] [Google Scholar]
  161. 161.
    Zingaropoli MA, Nijhawan P, Carraro A, Pasculli P, Zuccala P, et al. 2021.. Increased sCD163 and sCD14 plasmatic levels and depletion of peripheral blood pro-inflammatory monocytes, myeloid and plasmacytoid dendritic cells in patients with severe COVID-19 pneumonia. . Front. Immunol. 12::627548
    [Crossref] [Google Scholar]
  162. 162.
    Lee JS, Park S, Jeong HW, Ahn JY, Choi SJ, et al. 2020.. Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. . Sci. Immunol. 5::eabd1554
    [Crossref] [Google Scholar]
  163. 163.
    Lucas C, Wong P, Klein J, Castro TBR, Silva J, et al. 2020.. Longitudinal analyses reveal immunological misfiring in severe COVID-19. . Nature 584::46369
    [Crossref] [Google Scholar]
  164. 164.
    Sposito B, Broggi A, Pandolfi L, Crotta S, Clementi N, et al. 2021.. The interferon landscape along the respiratory tract impacts the severity of COVID-19. . Cell 184::495368.e16
    [Crossref] [Google Scholar]
  165. 165.
    Sun X, Gao C, Zhao K, Yang Y, Rassadkina Y, et al. 2022.. Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses. . Front. Immunol. 13::984553
    [Crossref] [Google Scholar]
  166. 166.
    Guo Y, Kasahara S, Jhingran A, Tosini NL, Zhai B, et al. 2020.. During Aspergillus infection, monocyte-derived DCs, neutrophils, and plasmacytoid DCs enhance innate immune defense through CXCR3-dependent crosstalk. . Cell Host Microbe 28::10416.e4
    [Crossref] [Google Scholar]
  167. 167.
    Kotov DI, Lee OV, Fattinger SA, Langner CA, Guillen JV, et al. 2023.. Early cellular mechanisms of type I interferon–driven susceptibility to tuberculosis. . Cell 186::553653.e22
    [Crossref] [Google Scholar]
  168. 168.
    Lee AM, Laurent P, Nathan CF, Barrat FJ. 2023.. Neutrophil-plasmacytoid dendritic cell interaction leads to production of type I IFN in response to Mycobacterium tuberculosis. . Eur. J. Immunol. https://doi.org/10.1002/eji.202350666
    [Google Scholar]
  169. 169.
    Daissormont IT, Christ A, Temmerman L, Sampedro Millares S, Seijkens T, et al. 2011.. Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity. . Circ. Res. 109::138795
    [Crossref] [Google Scholar]
  170. 170.
    Doring Y, Manthey HD, Drechsler M, Lievens D, Megens RT, et al. 2012.. Auto-antigenic protein–DNA complexes stimulate plasmacytoid dendritic cells to promote atherosclerosis. . Circulation 125::167383
    [Crossref] [Google Scholar]
  171. 171.
    Yun TJ, Lee JS, Machmach K, Shim D, Choi J, et al. 2016.. Indoleamine 2,3-dioxygenase-expressing aortic plasmacytoid dendritic cells protect against atherosclerosis by induction of regulatory T cells. . Cell Metab. 23::85266
    [Crossref] [Google Scholar]
  172. 172.
    Ghosh AR, Bhattacharya R, Bhattacharya S, Nargis T, Rahaman O, et al. 2016.. Adipose recruitment and activation of plasmacytoid dendritic cells fuel metaflammation. . Diabetes 65::344052
    [Crossref] [Google Scholar]
  173. 173.
    Li C, Wang G, Sivasami P, Ramirez RN, Zhang Y, et al. 2021.. Interferon-α-producing plasmacytoid dendritic cells drive the loss of adipose tissue regulatory T cells during obesity. . Cell Metab. 33::161023.e5
    [Crossref] [Google Scholar]
  174. 174.
    Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. 2001.. Plasmacytoid dendritic cells (natural interferon-α/β-producing cells) accumulate in cutaneous lupus erythematosus lesions. . Am. J. Pathol. 159::23743
    [Crossref] [Google Scholar]
  175. 175.
    Blomberg S, Eloranta M-L, Cederblad B, Nordlind K, Alm G, Rönnblom L. 2001.. Presence of cutaneous interferon-α producing cells in patients with systemic lupus erythematosus. . Lupus 10::48490
    [Crossref] [Google Scholar]
  176. 176.
    Ronnblom L, Alm GV. 2001.. A pivotal role for the natural interferon α–producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. . J. Exp. Med. 194::F5963
    [Crossref] [Google Scholar]
  177. 177.
    Caielli S, Wan Z, Pascual V. 2023.. Systemic lupus erythematosus pathogenesis: interferon and beyond. . Annu. Rev. Immunol. 41::53360
    [Crossref] [Google Scholar]
  178. 178.
    Lee PY, Kumagai Y, Li Y, Takeuchi O, Yoshida H, et al. 2008.. TLR7-dependent and FcγR-independent production of type I interferon in experimental mouse lupus. . J. Exp. Med. 205::29953006
    [Crossref] [Google Scholar]
  179. 179.
    Caielli S, Cardenas J, de Jesus AA, Baisch J, Walters L, et al. 2021.. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. . Cell 184::446479.e19
    [Crossref] [Google Scholar]
  180. 180.
    Sisirak V, Ganguly D, Lewis KL, Couillault C, Tanaka L, et al. 2014.. Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. . J. Exp. Med. 211::196976
    [Crossref] [Google Scholar]
  181. 181.
    Rowland SL, Riggs JM, Gilfillan S, Bugatti M, Vermi W, et al. 2014.. Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model. . J. Exp. Med. 211::197791
    [Crossref] [Google Scholar]
  182. 182.
    Davison LM, Jorgensen TN. 2015.. Sialic acid-binding immunoglobulin-type lectin H-positive plasmacytoid dendritic cells drive spontaneous lupus-like disease development in B6.Nba2 mice. . Arthritis Rheumatol. 67::101222
    [Crossref] [Google Scholar]
  183. 183.
    Soni C, Perez OA, Voss WN, Pucella JN, Serpas L, et al. 2020.. Plasmacytoid dendritic cells and type I interferon promote extrafollicular B cell responses to extracellular self-DNA. . Immunity 52::102238.e7
    [Crossref] [Google Scholar]
  184. 184.
    Ah Kioon MD, Tripodo C, Fernandez D, Kirou KA, Spiera RF, et al. 2018.. Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8. . Sci. Transl. Med. 10::eaam8458
    [Crossref] [Google Scholar]
  185. 185.
    Ross RL, Corinaldesi C, Migneco G, Carr IM, Antanaviciute A, et al. 2021.. Targeting human plasmacytoid dendritic cells through BDCA2 prevents skin inflammation and fibrosis in a novel xenotransplant mouse model of scleroderma. . Ann. Rheum. Dis. 80::92029
    [Crossref] [Google Scholar]
  186. 186.
    Li J, Ding H, Meng Y, Li G, Fu Q, et al. 2020.. Taurine metabolism aggravates the progression of lupus by promoting the function of plasmacytoid dendritic cells. . Arthritis Rheumatol. 72::210617
    [Crossref] [Google Scholar]
  187. 187.
    Meng Y, Ma J, Yao C, Ye Z, Ding H, et al. 2022.. The NCF1 variant p.R90H aggravates autoimmunity by facilitating the activation of plasmacytoid dendritic cells. . J. Clin. Investig. 132::e153619
    [Crossref] [Google Scholar]
  188. 188.
    Luo H, Urbonaviciute V, Saei AA, Lyu H, Gaetani M, et al. 2023.. NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions. . JCI Insight 8::e164875
    [Crossref] [Google Scholar]
  189. 189.
    Sakata K, Nakayamada S, Miyazaki Y, Kubo S, Ishii A, et al. 2018.. Up-regulation of TLR7-mediated IFN-α production by plasmacytoid dendritic cells in patients with systemic lupus erythematosus. . Front. Immunol. 9::1957
    [Crossref] [Google Scholar]
  190. 190.
    Psarras A, Alase A, Antanaviciute A, Carr IM, Md Yusof MY, et al. 2020.. Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity. . Nat. Commun. 11::6149
    [Crossref] [Google Scholar]
  191. 191.
    Chaudhary V, Ah Kioon MD, Hwang SM, Mishra B, Lakin K, et al. 2022.. Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses. . J. Exp. Med. 219::e20221085
    [Crossref] [Google Scholar]
  192. 192.
    Iwamoto T, Dorschner JM, Selvaraj S, Mezzano V, Jensen MA, et al. 2022.. High systemic type I interferon activity is associated with active class III/IV lupus nephritis. . J. Rheumatol. 49::38897
    [Crossref] [Google Scholar]
  193. 193.
    Domeier PP, Chodisetti SB, Schell SL, Kawasawa YI, Fasnacht MJ, et al. 2018.. B-cell-intrinsic type 1 interferon signaling is crucial for loss of tolerance and the development of autoreactive B cells. . Cell Rep. 24::40618
    [Crossref] [Google Scholar]
  194. 194.
    Bradford HF, Haljasmagi L, Menon M, McDonnell TCR, Sarekannu K, et al. 2023.. Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets. . Cell Rep. Med. 4::100894
    [Crossref] [Google Scholar]
  195. 195.
    Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J. 2003.. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. . Immunity 19::22534
    [Crossref] [Google Scholar]
  196. 196.
    van Bon L, Affandi AJ, Broen J, Christmann RB, Marijnissen RJ, et al. 2014.. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. . N. Engl. J. Med. 370::43343
    [Crossref] [Google Scholar]
  197. 197.
    Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, et al. 2020.. Trial of anifrolumab in active systemic lupus erythematosus. . N. Engl. J. Med. 382::21121
    [Crossref] [Google Scholar]
  198. 198.
    Schrezenmeier E, Dorner T. 2020.. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. . Nat. Rev. Rheumatol. 16::15566
    [Crossref] [Google Scholar]
  199. 199.
    Sacre K, Criswell LA, McCune JM. 2012.. Hydroxychloroquine is associated with impaired interferon-α and tumor necrosis factor α production by plasmacytoid dendritic cells in systemic lupus erythematosus. . Arthritis Res. Ther. 14::R155
    [Crossref] [Google Scholar]
  200. 200.
    Gardet A, Pellerin A, McCarl CA, Diwanji R, Wang W, et al. 2019.. Effect of in vivo hydroxychloroquine and ex vivo anti-BDCA2 mAb treatment on pDC IFNα production from patients affected with cutaneous lupus erythematosus. . Front. Immunol. 10::275
    [Crossref] [Google Scholar]
  201. 201.
    Conti F, Ceccarelli F, Perricone C, Massaro L, Cipriano E, et al. 2014.. Mycophenolate mofetil in systemic lupus erythematosus: results from a retrospective study in a large monocentric cohort and review of the literature. . Immunol. Res. 60::27076
    [Crossref] [Google Scholar]
  202. 202.
    Shigesaka M, Ito T, Inaba M, Imai K, Yamanaka H, et al. 2020.. Mycophenolic acid, the active form of mycophenolate mofetil, interferes with IRF7 nuclear translocation and type I IFN production by plasmacytoid dendritic cells. . Arthritis Res. Ther. 22::111
    [Crossref] [Google Scholar]
  203. 203.
    Dzionek A, Sohma Y, Nagafune J, Cella M, Colonna M, et al. 2001.. BDCA-2, a novel plasmacytoid dendritic cell–specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon α/β induction. . J. Exp. Med. 194::182334
    [Crossref] [Google Scholar]
  204. 204.
    Rissoan MC, Duhen T, Bridon JM, Bendriss-Vermare N, Peronne C, et al. 2002.. Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. . Blood 100::3295303
    [Crossref] [Google Scholar]
  205. 205.
    Furie R, Werth VP, Merola JF, Stevenson L, Reynolds TL, et al. 2019.. Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. . J. Clin. Investig. 129::135971
    [Crossref] [Google Scholar]
  206. 206.
    Werth VP, Furie RA, Romero-Diaz J, Navarra S, Kalunian K, et al. 2022.. Trial of anti-BDCA2 antibody litifilimab for cutaneous lupus erythematosus. . N. Engl. J. Med. 387::32131
    [Crossref] [Google Scholar]
  207. 207.
    Furie RA, van Vollenhoven RF, Kalunian K, Navarra S, Romero-Diaz J, et al. 2022.. Trial of anti-BDCA2 antibody litifilimab for systemic lupus erythematosus. . N. Engl. J. Med. 387::894904
    [Crossref] [Google Scholar]
  208. 208.
    Karnell JL, Wu Y, Mittereder N, Smith MA, Gunsior M, et al. 2021.. Depleting plasmacytoid dendritic cells reduces local type I interferon responses and disease activity in patients with cutaneous lupus. . Sci. Transl. Med. 13::eabf8442
    [Crossref] [Google Scholar]
  209. 209.
    Monaghan KA, Hoi A, Gamell C, Tai TY, Linggi B, et al. 2023.. CSL362 potently and specifically depletes pDCs invitro and ablates SLE–immune complex–induced IFN responses. . iScience 26::107173
    [Crossref] [Google Scholar]
  210. 210.
    Cai T, Gouble A, Black KL, Skwarska A, Naqvi AS, et al. 2022.. Targeting CD123 in blastic plasmacytoid dendritic cell neoplasm using allogeneic anti-CD123 CAR T cells. . Nat. Commun. 13::2228
    [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-immunol-090122-041105
Loading
/content/journals/10.1146/annurev-immunol-090122-041105
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error