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Annual Review of Immunology

Volume 41, 2023

Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond

Abstract

Autoreactive B cells and interferons are central players in systemic lupus erythematosus (SLE) pathogenesis. The partial success of drugs targeting these pathways, however, supports heterogeneity in upstream mechanisms contributing to disease pathogenesis. In this review, we focus on recent insights from genetic and immune monitoring studies of patients that are refining our understanding of these basic mechanisms. Among them, novel mutations in genes affecting intrinsic B cell activation or clearance of interferogenic nucleic acids have been described. Mitochondria have emerged as relevant inducers and/or amplifiers of SLE pathogenesis through a variety of mechanisms that include disruption of organelle integrity or compartmentalization, defective metabolism, and failure of quality control measures. These result in extra- or intracellular release of interferogenic nucleic acids as well as in innate and/or adaptive immune cell activation. A variety of classic and novel SLE autoantibody specificities have been found to recapitulate genetic alterations associated with monogenic lupus or to trigger interferogenic amplification loops. Finally, atypical B cells and novel extrafollicular T helper cell subsets have been proposed to contribute to the generation of SLE autoantibodies. Overall, these novel insights provide opportunities to deepen the immunophenotypic surveillance of patients and open the door to patient stratification and personalized, rational approaches to therapy.

Keyword(s): autoantibodies, cell death, extrafollicular, lupus, mitochondria
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2023-04-26
2024-04-28
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Literature Cited

  1. 1.
    Tsokos GC. 2011. Systemic lupus erythematosus. N. Engl. J. Med. 365:2110–21
     [Google Scholar]
  2. 2.
    Lazar S, Kahlenberg JM. 2023. Systemic lupus erythematosus: new diagnostic and therapeutic approaches. Annu. Rev. Med. 74:339–52
     [Google Scholar]
  3. 3.
    Hoi AY, Morand EF. 2021. Treatment update in systemic lupus erythematous. Rheum. Dis. Clin. N. Am. 47:513–30
     [Google Scholar]
  4. 4.
    Almlof JC, Nystedt S, Leonard D, Eloranta ML, Grosso G et al. 2019. Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus. Hum. Genet. 138:141–50
     [Google Scholar]
  5. 5.
    Bave U, Vallin H, Alm GV, Ronnblom L. 2001. Activation of natural interferon-alpha producing cells by apoptotic U937 cells combined with lupus IgG and its regulation by cytokines. J. Autoimmun. 17:71–80
     [Google Scholar]
  6. 6.
    Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD. 2005. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Investig. 115:407–17
     [Google Scholar]
  7. 7.
    Guiducci C, Gong M, Xu Z, Gill M, Chaussabel D et al. 2010. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 465:937–41
     [Google Scholar]
  8. 8.
    Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A. 2002. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416:603–7
     [Google Scholar]
  9. 9.
    Santini SM, Lapenta C, Logozzi M, Parlato S, Spada M et al. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J. Exp. Med. 191:1777–88
     [Google Scholar]
  10. 10.
    Le Bon A, Schiavoni G, D'Agostino G, Gresser I, Belardelli F, Tough DF 2001. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14:461–70
     [Google Scholar]
  11. 11.
    Pascual V, Farkas L, Banchereau J. 2006. Systemic lupus erythematosus: all roads lead to type I interferons. Curr. Opin. Immunol. 18:676–82
     [Google Scholar]
  12. 12.
    Looney RJ. 2010. B cell-targeted therapies for systemic lupus erythematosus: an update on clinical trial data. Drugs 70:529–40
     [Google Scholar]
  13. 13.
    Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA et al. 2011. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–31
     [Google Scholar]
  14. 14.
    Bruce IN, Furie RA, Morand EF, Manzi S, Tanaka Y et al. 2022. Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials. Ann. Rheum. Dis. 81:962–69
     [Google Scholar]
  15. 15.
    Crow YJ, Stetson DB. 2022. The type I interferonopathies: 10 years on. Nat. Rev. Immunol. 22:471–83
     [Google Scholar]
  16. 16.
    Belot A, Rice GI, Omarjee SO, Rouchon Q, Smith EMD et al. 2020. Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts. Lancet Rheumatol 2:E99–109 Correction. 2020 Lancet Rheumatol. 2:E644
     [Google Scholar]
  17. 17.
    Charras A, Haldenby S, Smith EMD, Egbivwie N, Olohan L et al. 2022. Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile-onset SLE. Rheumatology. In press. https://doi.org/10.1093/rheumatology/keac275
    [Google Scholar]
  18. 18.
    Sisirak V, Sally B, D'Agati V, Martinez-Ortiz W, Ozcakar ZB et al. 2016. Digestion of chromatin in apoptotic cell microparticles prevents autoimmunity. Cell 166:88–101
     [Google Scholar]
  19. 19.
    Jiang SH, Athanasopoulos V, Ellyard JI, Chuah A, Cappello J et al. 2019. Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus. Nat. Commun. 10:2201
     [Google Scholar]
  20. 20.
    Brown GJ, Canete PF, Wang H, Medhavy A, Bones J et al. 2022. TLR7 gain-of-function genetic variation causes human lupus. Nature 605:349–56
     [Google Scholar]
  21. 21.
    He Y, Gallman AE, Xie C, Shen Q, Ma J et al. 2022. P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance. J. Exp. Med. 219:1e20211004
     [Google Scholar]
  22. 22.
    Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K et al. 2007. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat. Genet. 39:1065–67
     [Google Scholar]
  23. 23.
    Briggs TA, Rice GI, Daly S, Urquhart J, Gornall H et al. 2011. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat. Genet. 43:127–31
     [Google Scholar]
  24. 24.
    An J, Briggs TA, Dumax-Vorzet A, Alarcon-Riquelme ME, Belot A et al. 2017. Tartrate-resistant acid phosphatase deficiency in the predisposition to systemic lupus erythematosus. Arthritis Rheum. 69:131–42
     [Google Scholar]
  25. 25.
    Ling GS, Crawford G, Buang N, Bartok I, Tian K et al. 2018. C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism. Science 360:558–63
     [Google Scholar]
  26. 26.
    Schejbel L, Skattum L, Hagelberg S, Ahlin A, Schiller B et al. 2011. Molecular basis of hereditary C1q deficiency—revisited: identification of several novel disease-causing mutations. Genes Immun. 12:626–34
     [Google Scholar]
  27. 27.
    Xu L, Zhao J, Sun Q, Xu X, Wang L et al. 2022. Loss-of-function variants in SAT1 cause X-linked childhood-onset systemic lupus erythematosus. Ann. Rheum. Dis. 81:121712–21
     [Google Scholar]
  28. 28.
    Ortíz-Fernández L, Martín J, Alarcón-Riquelme ME. 2022. A summary on the genetics of systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and Sjogren's syndrome. Clin. Rev. Allergy Immunol. In press
    [Google Scholar]
  29. 29.
    Langefeld CD, Ainsworth HC, Cunninghame Graham DS, Kelly JA, Comeau ME et al. 2017. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat. Commun. 8:16021
     [Google Scholar]
  30. 30.
    Nehar-Belaid D, Hong S, Marches R, Chen G, Bolisetty M et al. 2020. Mapping systemic lupus erythematosus heterogeneity at the single-cell level. Nat. Immunol. 21:1094–106
     [Google Scholar]
  31. 31.
    Banchereau R, Hong S, Cantarel B, Baldwin N, Baisch J et al. 2016. Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell 165:551–65
     [Google Scholar]
  32. 32.
    Perez RK, Gordon MG, Subramaniam M, Kim MC, Hartoularos GC et al. 2022. Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus. Science 376:eabf1970
     [Google Scholar]
  33. 33.
    Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y et al. 2019. The immune cell landscape in kidneys of patients with lupus nephritis. Nat. Immunol. 20:902–14
     [Google Scholar]
  34. 34.
    Fava A, Buyon J, Mohan C, Zhang T, Belmont HM et al. 2020. Integrated urine proteomics and renal single-cell genomics identify an IFN-gamma response gradient in lupus nephritis. JCI Insight 5:12e138345
     [Google Scholar]
  35. 35.
    Guthridge JM, Lu R, Tran LT, Arriens C, Aberle T et al. 2020. Adults with systemic lupus exhibit distinct molecular phenotypes in a cross-sectional study. EClinicalMedicine 20:100291
     [Google Scholar]
  36. 36.
    Nakano M, Ota M, Takeshima Y, Iwasaki Y, Hatano H et al. 2022. Distinct transcriptome architectures underlying lupus establishment and exacerbation. Cell 185:3375–89.e21
     [Google Scholar]
  37. 37.
    Dunlap GS, Billi AC, Xing X, Ma F, Maz MP et al. 2022. Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney. JCI Insight 7:8e156341
     [Google Scholar]
  38. 38.
    Billi AC, Ma F, Plazyo O, Gharaee-Kermani M, Wasikowski R et al. 2022. Nonlesional lupus skin contributes to inflammatory education of myeloid cells and primes for cutaneous inflammation. Sci. Transl. Med. 14:eabn2263
     [Google Scholar]
  39. 39.
    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. 382:211–21
     [Google Scholar]
  40. 40.
    Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV et al. 2018. Distinct effector B cells induced by unregulated Toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity 49:725–39.e6
     [Google Scholar]
  41. 41.
    Zumaquero E, Stone SL, Scharer CD, Jenks SA, Nellore A et al. 2019. IFNγ induces epigenetic programming of human T-bet(hi) B cells and promotes TLR7/8 and IL-21 induced differentiation. eLife 8:e41641
     [Google Scholar]
  42. 42.
    Caielli S, Veiga DT, Balasubramanian P, Athale S, Domic B et al. 2019. A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate. Nat. Med. 25:175–81
     [Google Scholar]
  43. 43.
    Munroe ME, Lu R, Zhao YD, Fife DA, Robertson JM et al. 2016. Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann. Rheum. Dis. 75:2014–21
     [Google Scholar]
  44. 44.
    Oke V, Gunnarsson I, Dorschner J, Eketjall S, Zickert A et al. 2019. High levels of circulating interferons type I, type II and type III associate with distinct clinical features of active systemic lupus erythematosus. Arthritis Res. Ther. 21:107
     [Google Scholar]
  45. 45.
    Boedigheimer MJ, Martin DA, Amoura Z, Sanchez-Guerrero J, Romero-Diaz J et al. 2017. Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-gamma monoclonal antibody, in SLE subjects without or with lupus nephritis. Lupus Sci. Med. 4:e000226
     [Google Scholar]
  46. 46.
    van Vollenhoven RF, Kalunian KC, Dörner T, Hahn BH, Tanaka Y et al. 2022. Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus. Ann. Rheum. Dis. 81:111556–63
     [Google Scholar]
  47. 47.
    Broggi A, Granucci F, Zanoni I. 2020. Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion. J. Exp. Med. 217:e20190295
     [Google Scholar]
  48. 48.
    Rumore PM, Steinman CR. 1990. Endogenous circulating DNA in systemic lupus erythematosus: occurrence as multimeric complexes bound to histone. J. Clin. Investig. 86:69–74
     [Google Scholar]
  49. 49.
    Galluzzi L, Yamazaki T, Kroemer G. 2018. Linking cellular stress responses to systemic homeostasis. Nat. Rev. Mol. Cell Biol. 19:731–45
     [Google Scholar]
  50. 50.
    Gullett JM, Tweedell RE, Kanneganti TD. 2022. It's all in the PAN: crosstalk, plasticity, redundancies, switches, and interconnectedness encompassed by PANoptosis underlying the totality of cell death-associated biological effects. Cells 11:1495
     [Google Scholar]
  51. 51.
    Chen Q, Wang J, Xiang M, Wang Y, Zhang Z et al. 2022. The potential role of ferroptosis in systemic lupus erythematosus. Front. Immunol. 13:855622
     [Google Scholar]
  52. 52.
    Hakkim A, Furnrohr BG, Amann K, Laube B, Abed UA et al. 2010. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. PNAS 107:9813–18
     [Google Scholar]
  53. 53.
    Doran AC, Yurdagul A Jr., Tabas I 2020. Efferocytosis in health and disease. Nat. Rev. Immunol. 20:254–67
     [Google Scholar]
  54. 54.
    Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35:495–516
     [Google Scholar]
  55. 55.
    Martin M, Blom AM. 2016. Complement in removal of the dead—balancing inflammation. Immunol. Rev. 274:218–32
     [Google Scholar]
  56. 56.
    Pisetsky D. 2017. The role of microparticles in the pathogenesis of SLE: a new look at an old paradigm. Lupus Sci. Med. 4:e000220
     [Google Scholar]
  57. 57.
    Ding SC, Lo YMD. 2022. Cell-Free DNA fragmentomics in liquid biopsy. Diagnostics 12:4978
     [Google Scholar]
  58. 58.
    Napirei M, Ludwig S, Mezrhab J, Klockl T, Mannherz HG. 2009. Murine serum nucleases—contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1-like 3 (DNase1l3). FEBS J. 276:1059–73
     [Google Scholar]
  59. 59.
    Napirei M, Wulf S, Eulitz D, Mannherz HG, Kloeckl T. 2005. Comparative characterization of rat deoxyribonuclease 1 (Dnase1) and murine deoxyribonuclease 1-like 3 (Dnase1l3). Biochem. J. 389:355–64
     [Google Scholar]
  60. 60.
    Wilber A, O'Connor TP, Lu ML, Karimi A, Schneider MC 2003. Dnase1l3 deficiency in lupus-prone MRL and NZB/W F1 mice. Clin. Exp. Immunol. 134:46–52
     [Google Scholar]
  61. 61.
    Chan RWY, Serpas L, Ni M, Volpi S, Hiraki LT et al. 2020. Plasma DNA profile associated with DNASE1L3 gene mutations: clinical observations, relationships to nuclease substrate preference, and in vivo correction. Am. J. Hum. Genet. 107:882–94
     [Google Scholar]
  62. 62.
    Serpas L, Chan RWY, Jiang P, Ni M, Sun K et al. 2019. Dnase1l3 deletion causes aberrations in length and end-motif frequencies in plasma DNA. PNAS 116:641–49
     [Google Scholar]
  63. 63.
    Odaka C, Mizuochi T. 1999. Role of macrophage lysosomal enzymes in the degradation of nucleosomes of apoptotic cells. J. Immunol. 163:5346–52
     [Google Scholar]
  64. 64.
    Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y et al. 2004. Neutrophil extracellular traps kill bacteria. Science 303:1532–35
     [Google Scholar]
  65. 65.
    Stetson DB, Ko JS, Heidmann T, Medzhitov R. 2008. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134:587–98
     [Google Scholar]
  66. 66.
    Ablasser A, Hemmerling I, Schmid-Burgk JL, Behrendt R, Roers A, Hornung V. 2014. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. J. Immunol. 192:5993–97
     [Google Scholar]
  67. 67.
    Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. 1992. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–17
     [Google Scholar]
  68. 68.
    Magerus A, Bercher-Brayer C, Rieux-Laucat F. 2021. The genetic landscape of the FAS pathway deficiencies. Biomed. J. 44:388–99
     [Google Scholar]
  69. 69.
    Al-Mayouf SM, Sunker A, Abdwani R, Abrawi SA, Almurshedi F et al. 2011. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat. Genet. 43:1186–88
     [Google Scholar]
  70. 70.
    Batu ED, Kosukcu C, Taskiran E, Sahin S, Akman S et al. 2018. Whole exome sequencing in early-onset systemic lupus erythematosus. J. Rheumatol. 45:1671–79
     [Google Scholar]
  71. 71.
    Carbonella A, Mancano G, Gremese E, Alkuraya FS, Patel N et al. 2017. An autosomal recessive DNASE1L3-related autoimmune disease with unusual clinical presentation mimicking systemic lupus erythematosus. Lupus 26:768–72
     [Google Scholar]
  72. 72.
    Ozcakar ZB, Foster J 2nd, Diaz-Horta O, Kasapcopur O, Fan YS et al. 2013. DNASE1L3 mutations in hypocomplementemic urticarial vasculitis syndrome. Arthritis Rheum. 65:2183–89
     [Google Scholar]
  73. 73.
    Ueki M, Takeshita H, Fujihara J, Iida R, Yuasa I et al. 2009. Caucasian-specific allele in non-synonymous single nucleotide polymorphisms of the gene encoding deoxyribonuclease I-like 3, potentially relevant to autoimmunity, produces an inactive enzyme. Clin. Chim. Acta 407:20–24
     [Google Scholar]
  74. 74.
    Acosta-Herrera M, Kerick M, Gonzalez-Serna D Myositis Genet. Consort., Scleroderma Genet. Consort. et al. 2019. Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases. Ann. Rheum. Dis. 78:311–19
     [Google Scholar]
  75. 75.
    Knight JS, Kaplan MJ. 2012. Lupus neutrophils: ‘NET’ gain in understanding lupus pathogenesis. Curr. Opin. Rheumatol. 24:441–50
     [Google Scholar]
  76. 76.
    Papayannopoulos V. 2018. Neutrophil extracellular traps in immunity and disease. Nat. Rev. Immunol. 18:134–47
     [Google Scholar]
  77. 77.
    Soni C, Reizis B. 2019. Self-DNA at the epicenter of SLE: immunogenic forms, regulation, and effects. Front. Immunol. 10:1601
     [Google Scholar]
  78. 78.
    Li P, Jiang M, Li K, Li H, Zhou Y et al. 2021. Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity. Nat. Immunol. 22:1107–17
     [Google Scholar]
  79. 79.
    Kawane K, Motani K, Nagata S. 2014. DNA degradation and its defects. Cold Spring Harb. Perspect. Biol. 6:a016394
     [Google Scholar]
  80. 80.
    Rodero MP, Tesser A, Bartok E, Rice GI, Della Mina E et al. 2017. Type I interferon-mediated autoinflammation due to DNase II deficiency. Nat. Commun. 8:2176
     [Google Scholar]
  81. 81.
    Livingston JH, Crow YJ. 2016. Neurologic phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi–Goutières syndrome and beyond. Neuropediatrics 47:355–60
     [Google Scholar]
  82. 82.
    Rice GI, Rodero MP, Crow YJ. 2015. Human disease phenotypes associated with mutations in TREX1. J. Clin. Immunol. 35:235–43
     [Google Scholar]
  83. 83.
    Omarjee O, Picard C, Frachette C, Moreews M, Rieux-Laucat F et al. 2019. Monogenic lupus: dissecting heterogeneity. Autoimmun. Rev. 18:102361
     [Google Scholar]
  84. 84.
    Riley JS, Tait SW. 2020. Mitochondrial DNA in inflammation and immunity. EMBO Rep. 21:e49799
     [Google Scholar]
  85. 85.
    Becker Y, Marcoux G, Allaeys I, Julien AS, Loignon RC et al. 2019. Autoantibodies in systemic lupus erythematosus target mitochondrial RNA. Front. Immunol. 10:1026
     [Google Scholar]
  86. 86.
    Petri M. 2020. Antiphospholipid syndrome. Transl. Res. 225:70–81
     [Google Scholar]
  87. 87.
    Dieude M, Senecal JL, Raymond Y. 2004. Induction of endothelial cell apoptosis by heat-shock protein 60-reactive antibodies from anti-endothelial cell autoantibody-positive systemic lupus erythematosus patients. Arthritis Rheum. 50:3221–31
     [Google Scholar]
  88. 88.
    Becker YLC, Gagne JP, Julien AS, Levesque T, Allaeys I et al. 2022. Identification of mitofusin 1 and complement component 1q subcomponent binding protein as mitochondrial targets in systemic lupus erythematosus. Arthritis Rheum. 74:1193–203
     [Google Scholar]
  89. 89.
    Pisetsky DS, Spencer DM, Mobarrez F, Fuzzi E, Gunnarsson I, Svenungsson E. 2020. The binding of SLE autoantibodies to mitochondria. Clin. Immunol. 212:108349
     [Google Scholar]
  90. 90.
    Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM et al. 2008. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat. Med. 14:949–53
     [Google Scholar]
  91. 91.
    Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon HU. 2009. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ. 16:1438–44
     [Google Scholar]
  92. 92.
    Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS et al. 2016. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat. Med. 22:146–53
     [Google Scholar]
  93. 93.
    Garcia-Romo GS, Caielli S, Vega B, Connolly J, Allantaz F et al. 2011. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci. Transl. Med. 3:73ra20
     [Google Scholar]
  94. 94.
    Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J et al. 2003. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J. Exp. Med. 197:711–23
     [Google Scholar]
  95. 95.
    Caielli S, Athale S, Domic B, Murat E, Chandra M et al. 2016. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J. Exp. Med. 213:697–713
     [Google Scholar]
  96. 96.
    Jiao H, Jiang D, Hu X, Du W, Ji L et al. 2021. Mitocytosis, a migrasome-mediated mitochondrial quality-control process. Cell 184:2896–910.e13
     [Google Scholar]
  97. 97.
    Boudreau LH, Duchez AC, Cloutier N, Soulet D, Martin N et al. 2014. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood 124:2173–83
     [Google Scholar]
  98. 98.
    Linge P, Fortin PR, Lood C, Bengtsson AA, Boilard E. 2018. The non-haemostatic role of platelets in systemic lupus erythematosus. Nat. Rev. Rheumatol. 14:195–213
     [Google Scholar]
  99. 99.
    West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM et al. 2015. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520:553–57
     [Google Scholar]
  100. 100.
    Wu Z, Oeck S, West AP, Mangalhara KC, Sainz AG et al. 2019. Mitochondrial DNA stress signalling protects the nuclear genome. Nat. Metab. 1:1209–18
     [Google Scholar]
  101. 101.
    Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A et al. 2019. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science 366:1531–36
     [Google Scholar]
  102. 102.
    Dhir A, Dhir S, Borowski LS, Jimenez L, Teitell M et al. 2018. Mitochondrial double-stranded RNA triggers antiviral signalling in humans. Nature 560:238–42
     [Google Scholar]
  103. 103.
    Tigano M, Vargas DC, Tremblay-Belzile S, Fu Y, Sfeir A. 2021. Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance. Nature 591:477–81
     [Google Scholar]
  104. 104.
    Rai P, Janardhan KS, Meacham J, Madenspacher JH, Lin WC et al. 2021. IRGM1 links mitochondrial quality control to autoimmunity. Nat. Immunol. 22:312–21
     [Google Scholar]
  105. 105.
    Buskiewicz IA, Montgomery T, Yasewicz EC, Huber SA, Murphy MP et al. 2016. Reactive oxygen species induce virus-independent MAVS oligomerization in systemic lupus erythematosus. Sci. Signal. 9:ra115
     [Google Scholar]
  106. 106.
    Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM et al. 2017. Molecular definitions of autophagy and related processes. EMBO J. 36:1811–36
     [Google Scholar]
  107. 107.
    Zhou XJ, Lu XL, Lv JC, Yang HZ, Qin LX et al. 2011. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann. Rheum. Dis. 70:1330–37
     [Google Scholar]
  108. 108.
    Zhang YM, Cheng FJ, Zhou XJ, Qi YY, Zhao MH, Zhang H. 2015. Rare variants of ATG5 are likely to be associated with Chinese patients with systemic lupus erythematosus. Medicine 94:e939
     [Google Scholar]
  109. 109.
    Caza TN, Talaber G, Perl A 2012. Metabolic regulation of organelle homeostasis in lupus T cells. Clin. Immunol. 144:200–13
     [Google Scholar]
  110. 110.
    Perl A. 2013. Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Nat. Rev. Rheumatol. 9:674–86
     [Google Scholar]
  111. 111.
    Caza TN, Fernandez DR, Talaber G, Oaks Z, Haas M et al. 2014. HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE. Ann. Rheum. Dis. 73:1888–97
     [Google Scholar]
  112. 112.
    Chen PM, Katsuyama E, Satyam A, Li H, Rubio J et al. 2022. CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy. Sci. Adv. 8:eabo4271
     [Google Scholar]
  113. 113.
    Buang N, Tapeng L, Gray V, Sardini A, Whilding C et al. 2021. Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus. Nat. Commun. 12:1980
     [Google Scholar]
  114. 114.
    Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J. 2001. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294:1540–43
     [Google Scholar]
  115. 115.
    Gkirtzimanaki K, Kabrani E, Nikoleri D, Polyzos A, Blanas A et al. 2018. IFNα impairs autophagic degradation of mtDNA promoting autoreactivity of SLE monocytes in a STING-dependent fashion. Cell Rep. 25:921–33.e5
     [Google Scholar]
  116. 116.
    Morishita H, Eguchi T, Tsukamoto S, Sakamaki Y, Takahashi S et al. 2021. Organelle degradation in the lens by PLAAT phospholipases. Nature 592:634–38
     [Google Scholar]
  117. 117.
    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 184:4464–79.e19
     [Google Scholar]
  118. 118.
    Zhang J, Ney PA. 2010. Reticulocyte mitophagy: monitoring mitochondrial clearance in a mammalian model. Autophagy 6:405–8
     [Google Scholar]
  119. 119.
    van den Akker E, Satchwell TJ, Pellegrin S, Daniels G, Toye AM. 2010. The majority of the in vitro erythroid expansion potential resides in CD34− cells, outweighing the contribution of CD34+ cells and significantly increasing the erythroblast yield from peripheral blood samples. Haematologica 95:1594–98
     [Google Scholar]
  120. 120.
    Sugiura A, McLelland GL, Fon EA, McBride HM. 2014. A new pathway for mitochondrial quality control: mitochondrial-derived vesicles. EMBO J. 33:2142–56
     [Google Scholar]
  121. 121.
    Nolfi-Donegan D, Braganza A, Shiva S. 2020. Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement. Redox. Biol. 37:101674
     [Google Scholar]
  122. 122.
    Fritsch SD, Weichhart T. 2016. Effects of interferons and viruses on metabolism. Front. Immunol. 7:630
     [Google Scholar]
  123. 123.
    Wu D, Sanin DE, Everts B, Chen Q, Qiu J et al. 2016. Type 1 interferons induce changes in core metabolism that are critical for immune function. Immunity 44:1325–36
     [Google Scholar]
  124. 124.
    van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC et al. 2012. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36:68–78
     [Google Scholar]
  125. 125.
    Manderson AP, Botto M, Walport MJ. 2004. The role of complement in the development of systemic lupus erythematosus. Annu. Rev. Immunol. 22:431–56
     [Google Scholar]
  126. 126.
    Mills EL, Kelly B, Logan A, Costa ASH, Varma M et al. 2016. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167:457–70.e13
     [Google Scholar]
  127. 127.
    Weinberg SE, Singer BD, Steinert EM, Martinez CA, Mehta MM et al. 2019. Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature 565:495–99
     [Google Scholar]
  128. 128.
    Mills E, O'Neill LA. 2014. Succinate: a metabolic signal in inflammation. Trends Cell Biol. 24:313–20
     [Google Scholar]
  129. 129.
    Chen PM, Wilson PC, Shyer JA, Veselits M, Steach HR et al. 2020. Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis. Sci. Transl. Med. 12:eaay1620
     [Google Scholar]
  130. 130.
    Vyshkina T, Sylvester A, Sadiq S, Bonilla E, Canter JA et al. 2008. Association of common mitochondrial DNA variants with multiple sclerosis and systemic lupus erythematosus. Clin. Immunol. 129:31–35
     [Google Scholar]
  131. 131.
    Perry DJ, Yin Y, Telarico T, Baker HV, Dozmorov I et al. 2012. Murine lupus susceptibility locus Sle1c2 mediates CD4+ T cell activation and maps to estrogen-related receptor γ. J. Immunol. 189:793–803
     [Google Scholar]
  132. 132.
    Peace CG, O'Neill LA. 2022. The role of itaconate in host defense and inflammation. J. Clin. Investig. 132:2e148548
     [Google Scholar]
  133. 133.
    Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E et al. 2018. Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature 556:501–4
     [Google Scholar]
  134. 134.
    Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D et al. 2018. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556:113–17
     [Google Scholar]
  135. 135.
    Tang C, Wang X, Xie Y, Cai X, Yu N et al. 2018. 4-Octyl itaconate activates Nrf2 signaling to inhibit pro-inflammatory cytokine production in peripheral blood mononuclear cells of systemic lupus erythematosus patients. Cell Physiol. Biochem. 51:979–90
     [Google Scholar]
  136. 136.
    Lee SY, Lee SH, Yang EJ, Kim EK, Kim JK et al. 2015. Metformin ameliorates inflammatory bowel disease by suppression of the STAT3 signaling pathway and regulation of the between Th17/Treg balance. PLOS ONE 10:e0135858
     [Google Scholar]
  137. 137.
    Yin Y, Choi SC, Xu Z, Perry DJ, Seay H et al. 2015. Normalization of CD4+ T cell metabolism reverses lupus. Sci. Transl. Med. 7:274ra18
     [Google Scholar]
  138. 138.
    Titov AA, Baker HV, Brusko TM, Sobel ES, Morel L. 2019. Metformin inhibits the type 1 IFN response in human CD4+ T cells. J. Immunol. 203:338–48
     [Google Scholar]
  139. 139.
    Wang H, Li T, Chen S, Gu Y, Ye S. 2015. Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-of-concept trial of metformin. Arthritis Rheum. 67:3190–200
     [Google Scholar]
  140. 140.
    Sun F, Geng S, Wang H, Wang H, Liu Z et al. 2020. Effects of metformin on disease flares in patients with systemic lupus erythematosus: post hoc analyses from two randomised trials. Lupus Sci. Med. 7:e000429
     [Google Scholar]
  141. 141.
    Tian J, Avalos AM, Mao SY, Chen B, Senthil K et al. 2007. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat. Immunol. 8:487–96
     [Google Scholar]
  142. 142.
    Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH et al. 2007. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449:564–69
     [Google Scholar]
  143. 143.
    Lande R, Palazzo R, Gestermann N, Jandus C, Falchi M et al. 2020. Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus. Sci. Rep. 10:5851
     [Google Scholar]
  144. 144.
    Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. 2005. Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum. 52:1491–503
     [Google Scholar]
  145. 145.
    Hanaoka H, Iida H, Kiyokawa T, Takakuwa Y, Kawahata K. 2018. A positive direct Coombs' test in the absence of hemolytic anemia predicts high disease activity and poor renal response in systemic lupus erythematosus. Lupus 27:2274–78
     [Google Scholar]
  146. 146.
    Yeh TM, Chang HC, Liang CC, Wu JJ, Liu MF. 2003. Deoxyribonuclease-inhibitory antibodies in systemic lupus erythematosus. J. Biomed. Sci. 10:544–51
     [Google Scholar]
  147. 147.
    Emlen W, Ansari R, Burdick G. 1984. DNA-anti-DNA immune complexes. Antibody protection of a discrete DNA fragment from DNase digestion in vitro. J. Clin. Investig. 74:185–90
     [Google Scholar]
  148. 148.
    Hartl J, Serpas L, Wang Y, Rashidfarrokhi A, Perez OA et al. 2021. Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus. J. Exp. Med. 218:e20201138
     [Google Scholar]
  149. 149.
    Leffler J, Bengtsson AA, Blom AM. 2014. The complement system in systemic lupus erythematosus: an update. Ann. Rheum. Dis. 73:1601–6
     [Google Scholar]
  150. 150.
    Howe HS, Leung BPL. 2019. Anti-cytokine autoantibodies in systemic lupus erythematosus. Cells 9:172
     [Google Scholar]
  151. 151.
    Slavikova M, Schmeisser H, Kontsekova E, Mateicka F, Borecky L, Kontsek P. 2003. Incidence of autoantibodies against type I and type II interferons in a cohort of systemic lupus erythematosus patients in Slovakia. J. Interferon Cytokine Res. 23:143–47
     [Google Scholar]
  152. 152.
    Morimoto AM, Flesher DT, Yang J, Wolslegel K, Wang X et al. 2011. Association of endogenous anti-interferon-alpha autoantibodies with decreased interferon-pathway and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 63:2407–15
     [Google Scholar]
  153. 153.
    Gupta S, Tatouli IP, Rosen LB, Hasni S, Alevizos I et al. 2016. Distinct functions of autoantibodies against interferon in systemic lupus erythematosus: a comprehensive analysis of anticytokine autoantibodies in common rheumatic diseases. Arthritis Rheum. 68:1677–87
     [Google Scholar]
  154. 154.
    Tusseau M, Belot A. 2022. “P2RY8-son” break of tolerance promotes SLE. J. Exp. Med. 219:e20211972
     [Google Scholar]
  155. 155.
    Jiang SH, Stanley M, Vinuesa CG. 2020. Rare genetic variants in systemic autoimmunity. Immunol. Cell Biol. 98:490–99
     [Google Scholar]
  156. 156.
    Kuehn HS, Niemela JE, Rangel-Santos A, Zhang M, Pittaluga S et al. 2013. Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. Blood 121:3117–25
     [Google Scholar]
  157. 157.
    Victora GD, Nussenzweig MC. 2022. Germinal centers. Annu. Rev. Immunol. 40:413–42
     [Google Scholar]
  158. 158.
    Winkler TH, Fehr H, Kalden JR. 1992. Analysis of immunoglobulin variable region genes from human IgG anti-DNA hybridomas. Eur. J. Immunol. 22:1719–28
     [Google Scholar]
  159. 159.
    van Es JH, Gmelig Meyling FH, van de Akker WR, Aanstoot H, Derksen RH, Logtenberg T 1991. Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus. J. Exp. Med. 173:461–70
     [Google Scholar]
  160. 160.
    McCarty GA, Rice JR, Bembe ML, Pisetsky DS. 1982. Independent expression of autoantibodies in systemic lupus erythematosus. J. Rheumatol. 9:691–95
     [Google Scholar]
  161. 161.
    McCune WJ, Golbus J, Zeldes W, Bohlke P, Dunne R, Fox DA. 1988. Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. N. Engl. J. Med. 318:1423–31
     [Google Scholar]
  162. 162.
    William J, Euler C, Christensen S, Shlomchik MJ. 2002. Evolution of autoantibody responses via somatic hypermutation outside of germinal centers. Science 297:2066–70
     [Google Scholar]
  163. 163.
    Herlands RA, William J, Hershberg U, Shlomchik MJ. 2007. Anti-chromatin antibodies drive in vivo antigen-specific activation and somatic hypermutation of rheumatoid factor B cells at extrafollicular sites. Eur. J. Immunol. 37:3339–51
     [Google Scholar]
  164. 164.
    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 52:1022–38.e7
     [Google Scholar]
  165. 165.
    Woodruff MC, Ramonell RP, Nguyen DC, Cashman KS, Saini AS et al. 2020. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nat. Immunol. 21:1506–16
     [Google Scholar]
  166. 166.
    Kaneko N, Kuo HH, Boucau J, Farmer JR, Allard-Chamard H et al. 2020. Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell 183:143–57.e13
     [Google Scholar]
  167. 167.
    Elsner RA, Shlomchik MJ. 2020. Germinal center and extrafollicular B cell responses in vaccination, immunity, and autoimmunity. Immunity 53:1136–50
     [Google Scholar]
  168. 168.
    Jenks SA, Cashman KS, Woodruff MC, Lee FE, Sanz I. 2019. Extrafollicular responses in humans and SLE. Immunol. Rev. 288:136–48
     [Google Scholar]
  169. 169.
    Tipton CM, Fucile CF, Darce J, Chida A, Ichikawa T et al. 2015. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat. Immunol. 16:755–65
     [Google Scholar]
  170. 170.
    Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ et al. 2011. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c+ B-cell population is important for the development of autoimmunity. Blood 118:1305–15
     [Google Scholar]
  171. 171.
    Hao Y, O'Neill P, Naradikian MS, Scholz JL, Cancro MP. 2011. A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood 118:1294–304
     [Google Scholar]
  172. 172.
    Rubtsova K, Rubtsov AV, Thurman JM, Mennona JM, Kappler JW, Marrack P. 2017. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J. Clin. Investig. 127:1392–404
     [Google Scholar]
  173. 173.
    Liu Y, Zhou S, Qian J, Wang Y, Yu X et al. 2017. T-bet+CD11c+ B cells are critical for antichromatin immunoglobulin G production in the development of lupus. Arthritis Res. Ther. 19:225
     [Google Scholar]
  174. 174.
    Wang S, Wang J, Kumar V, Karnell JL, Naiman B et al. 2018. IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE. Nat. Commun. 9:1758
     [Google Scholar]
  175. 175.
    Portugal S, Tipton CM, Sohn H, Kone Y, Wang J et al. 2015. Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. eLife 4:e07218
     [Google Scholar]
  176. 176.
    Weiss GE, Crompton PD, Li S, Walsh LA, Moir S et al. 2009. Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area. J. Immunol. 183:2176–82
     [Google Scholar]
  177. 177.
    Moir S, Ho J, Malaspina A, Wang W, DiPoto AC et al. 2008. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J. Exp. Med. 205:1797–805
     [Google Scholar]
  178. 178.
    Lau D, Lan LY, Andrews SF, Henry C, Rojas KT et al. 2017. Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation. Sci. Immunol. 2:eaai8153
     [Google Scholar]
  179. 179.
    Yang R, Avery DT, Jackson KJL, Ogishi M, Benhsaien I et al. 2022. Human T-bet governs the generation of a distinct subset of CD11chighCD21low B cells. Sci. Immunol. 7:eabq3277
     [Google Scholar]
  180. 180.
    Keller B, Strohmeier V, Harder I, Unger S, Payne KJ et al. 2021. The expansion of human T-bethighCD21low B cells is T cell dependent. Sci. Immunol. 6:eabh0891
     [Google Scholar]
  181. 181.
    Rincon-Arevalo H, Wiedemann A, Stefanski AL, Lettau M, Szelinski F et al. 2021. Deep phenotyping of CD11c+ B cells in systemic autoimmunity and controls. Front. Immunol. 12:635615
     [Google Scholar]
  182. 182.
    Dominguez CX, Amezquita RA, Guan T, Marshall HD, Joshi NS et al. 2015. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. J. Exp. Med. 212:2041–56
     [Google Scholar]
  183. 183.
    Xu H, Chaudhri VK, Wu Z, Biliouris K, Dienger-Stambaugh K et al. 2015. Regulation of bifurcating B cell trajectories by mutual antagonism between transcription factors IRF4 and IRF8. Nat. Immunol. 16:1274–81
     [Google Scholar]
  184. 184.
    Luo W, Mayeux J, Gutierrez T, Russell L, Getahun A et al. 2014. A balance between B cell receptor and inhibitory receptor signaling controls plasma cell differentiation by maintaining optimal Ets1 levels. J. Immunol. 193:909–20
     [Google Scholar]
  185. 185.
    Liu X, Zhao Y, Qi H. 2022. T-independent antigen induces humoral memory through germinal centers. J. Exp. Med. 219:e20210527
     [Google Scholar]
  186. 186.
    Qi H, Cannons JL, Klauschen F, Schwartzberg PL, Germain RN. 2008. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455:764–69
     [Google Scholar]
  187. 187.
    Manni M, Gupta S, Ricker E, Chinenov Y, Park SH et al. 2018. Regulation of age-associated B cells by IRF5 in systemic autoimmunity. Nat. Immunol. 19:407–19
     [Google Scholar]
  188. 188.
    Rao DA, Gurish MF, Marshall JL, Slowikowski K, Fonseka CY et al. 2017. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature 542:110–14
     [Google Scholar]
  189. 189.
    Bocharnikov AV, Keegan J, Wacleche VS, Cao Y, Fonseka CY et al. 2019. PD-1hiCXCR5− T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI Insight 4:e130062
     [Google Scholar]
  190. 190.
    Rodda LB, Morawski PA, Pruner KB, Fahning ML, Howard CA et al. 2022. Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity. Cell 185:1588–601.e14
     [Google Scholar]
  191. 191.
    Collora JA, Liu R, Pinto-Santini D, Ravindra N, Ganoza C et al. 2022. Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity 55:1013–31.e7
     [Google Scholar]
  192. 192.
    Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N et al. 2020. Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus. PNAS 117:7305–16
     [Google Scholar]
  193. 193.
    Gregori S, Goudy KS, Roncarolo MG. 2012. The cellular and molecular mechanisms of immuno-suppression by human type 1 regulatory T cells. Front. Immunol. 3:30
     [Google Scholar]
  194. 194.
    Song Y, Wang N, Chen L, Fang L 2021. Tr1 cells as a key regulator for maintaining immune homeostasis in transplantation. Front. Immunol. 12:671579
     [Google Scholar]
  195. 195.
    Gagliani N, Magnani CF, Huber S, Gianolini ME, Pala M et al. 2013. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat. Med. 19:739–46
     [Google Scholar]
  196. 196.
    Bonnal RJP, Rossetti G, Lugli E, De Simone M, Gruarin P et al. 2021. Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression. Nat. Immunol. 22:735–45
     [Google Scholar]
  197. 197.
    Cope A, Le Friec G, Cardone J, Kemper C 2011. The Th1 life cycle: molecular control of IFN-gamma to IL-10 switching. Trends Immunol. 32:278–86
     [Google Scholar]
  198. 198.
    Stein K, Hummel M, Korbjuhn P, Foss HD, Anagnostopoulos I et al. 1999. Monocytoid B cells are distinct from splenic marginal zone cells and commonly derive from unmutated naive B cells and less frequently from postgerminal center B cells by polyclonal transformation. Blood 94:2800–8
     [Google Scholar]
  199. 199.
    Ehrhardt GR, Hijikata A, Kitamura H, Ohara O, Wang JY, Cooper MD. 2008. Discriminating gene expression profiles of memory B cell subpopulations. J. Exp. Med. 205:1807–17
     [Google Scholar]
  200. 200.
    Karin N. 2020. CXCR3 ligands in cancer and autoimmunity, chemoattraction of effector T cells, and beyond. Front. Immunol. 11:976
     [Google Scholar]
  201. 201.
    Herlands RA, Christensen SR, Sweet RA, Hershberg U, Shlomchik MJ. 2008. T cell-independent and Toll-like receptor-dependent antigen-driven activation of autoreactive B cells. Immunity 29:249–60
     [Google Scholar]
  202. 202.
    Sweet RA, Ols ML, Cullen JL, Milam AV, Yagita H, Shlomchik MJ. 2011. Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo. PNAS 108:7932–37
     [Google Scholar]
  203. 203.
    Lu E, Wolfreys FD, Muppidi JR, Xu Y, Cyster JG. 2019. S-Geranylgeranyl-l-glutathione is a ligand for human B cell-confinement receptor P2RY8. Nature 567:244–48
     [Google Scholar]
  204. 204.
    Muppidi JR, Schmitz R, Green JA, Xiao W, Larsen AB et al. 2014. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature 516:254–58
     [Google Scholar]
  205. 205.
    Wu C, Macleod I, Su AI. 2013. BioGPS and MyGene.info: organizing online, gene-centric information. Nucleic Acids Res. 41:D561–65
     [Google Scholar]
  206. 206.
    Toyama H, Okada S, Hatano M, Takahashi Y, Takeda N et al. 2002. Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells. Immunity 17:329–39
     [Google Scholar]
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Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond
Annual Review of Immunology 41, 533 (2023); https://doi.org/10.1146/annurev-immunol-101921-042422
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