1932

Abstract

Tissue-resident immune cells span both myeloid and lymphoid cell lineages, have been found in multiple human tissues, and play integral roles at all stages of the immune response, from maintaining homeostasis to responding to infectious challenges to resolution of inflammation to tissue repair. In humans, studying immune cells and responses in tissues is challenging, although recent advances in sampling and high-dimensional profiling have provided new insights into the ontogeny, maintenance, and functional role of tissue-resident immune cells. Each tissue contains a specific complement of resident immune cells. Moreover, resident immune cells for each lineage share core properties, along with tissue-specific adaptations. Here we propose a five-point checklist for defining resident immune cell types in humans and describe the currently known features of resident immune cells, their mechanisms of development, and their putative functional roles within various human organs. We also consider these aspects of resident immune cells in the context of future studies and therapeutics.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-093019-112809
2022-04-26
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/immunol/40/1/annurev-immunol-093019-112809.html?itemId=/content/journals/10.1146/annurev-immunol-093019-112809&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Worbs T, Hammerschmidt SI, Förster R. 2017. Dendritic cell migration in health and disease. Nat. Rev. Immunol. 17:130–48
    [Google Scholar]
  2. 2. 
    Schenkel JM, Masopust D. 2014. Tissue-resident memory T cells. Immunity 41:886–97
    [Google Scholar]
  3. 3. 
    Turner DL, Farber DL. 2014. Mucosal resident memory CD4 T cells in protection and immunopathology. Front. Immunol. 5:331
    [Google Scholar]
  4. 4. 
    Weisel NM, Weisel FJ, Farber DL, Borghesi LA, Shen Y et al. 2020. Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype. Blood 136:2774–85
    [Google Scholar]
  5. 5. 
    Kumar BV, Ma W, Miron M, Granot T, Guyer RS et al. 2017. Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep 20:2921–34
    [Google Scholar]
  6. 6. 
    Szabo PA, Levitin HM, Miron M, Snyder ME, Senda T et al. 2019. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease. Nat. Commun. 10:4706
    [Google Scholar]
  7. 7. 
    Szabo PA, Miron M, Farber DL. 2019. Location, location, location: tissue resident memory T cells in mice and humans. Sci. Immunol. 4:eaas9673
    [Google Scholar]
  8. 8. 
    Kumar BV, Connors TJ, Farber DL. 2018. Human T cell development, localization, and function throughout life. Immunity 48:202–13
    [Google Scholar]
  9. 9. 
    Weisberg SP, Carpenter DJ, Chait M, Dogra P, Gartrell-Corrado RD et al. 2019. Tissue-resident memory T cells mediate immune homeostasis in the human pancreas through the PD-1/PD-L1 pathway. Cell Rep 29:3916–32.e5
    [Google Scholar]
  10. 10. 
    Weisberg SP, Ural BB, Farber DL. 2021. Tissue-specific immunity for a changing world. Cell 184:1517–29
    [Google Scholar]
  11. 11. 
    Masopust D, Soerens AG. 2019. Tissue-resident T cells and other resident leukocytes. Annu. Rev. Immunol. 37:521–46
    [Google Scholar]
  12. 12. 
    Steinert EM, Schenkel JM, Fraser KA, Beura LK, Manlove LS et al. 2015. Quantifying memory CD8 T cells reveals regionalization of immunosurveillance. Cell 161:737–49
    [Google Scholar]
  13. 13. 
    Teichmann LL, Kashgarian M, Weaver CT, Roers A, Muller W, Shlomchik MJ. 2012. B cell-derived IL-10 does not regulate spontaneous systemic autoimmunity in MRL.Faslpr mice. J. Immunol. 188:678–85
    [Google Scholar]
  14. 14. 
    Teijaro JR, Turner D, Pham Q, Wherry EJ, Lefrancois L, Farber DL 2011. Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J. Immunol. 187:5510–14
    [Google Scholar]
  15. 15. 
    Ginhoux F, Jung S 2014. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 14:392–404
    [Google Scholar]
  16. 16. 
    Mackay LK, Kallies A. 2017. Transcriptional regulation of tissue-resident lymphocytes. Trends Immunol 38:94–103
    [Google Scholar]
  17. 17. 
    Mackay LK, Minnich M, Kragten NA, Liao Y, Nota B et al. 2016. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 352:459–63
    [Google Scholar]
  18. 18. 
    Milner JJ, Toma C, Yu B, Zhang K, Omilusik K et al. 2017. Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours. Nature 552:253–57
    [Google Scholar]
  19. 19. 
    Zundler S, Becker E, Spocinska M, Slawik M, Parga-Vidal L et al. 2019. Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation. Nat. Immunol. 20:288–300
    [Google Scholar]
  20. 20. 
    Ginhoux F, Guilliams M. 2016. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44:439–49
    [Google Scholar]
  21. 21. 
    Carpenter DJ, Granot T, Matsuoka N, Senda T, Kumar BV et al. 2018. Human immunology studies using organ donors: impact of clinical variations on immune parameters in tissues and circulation. Am. J. Transplant. 18:74–88
    [Google Scholar]
  22. 22. 
    Poon MML, Farber DL. 2020. The whole body as the system in systems immunology. iScience 23:101509
    [Google Scholar]
  23. 23. 
    Farber DL. 2021. Tissues, not blood, are where immune cells act. Nature 593:506–9
    [Google Scholar]
  24. 24. 
    Vieira Braga FA, Kar G, Berg M, Carpaij OA, Polanski K et al. 2019. A cellular census of human lungs identifies novel cell states in health and in asthma. Nat. Med. 25:1153–63
    [Google Scholar]
  25. 25. 
    Vantourout P, Hayday A. 2013. Six-of-the-best: unique contributions of γδ T cells to immunology. Nat. Rev. Immunol. 13:88–100
    [Google Scholar]
  26. 26. 
    Provine NM, Klenerman P. 2020. MAIT cells in health and disease. Annu. Rev. Immunol. 38:203–28
    [Google Scholar]
  27. 27. 
    Blériot C, Chakarov S, Ginhoux F 2020. Determinants of resident tissue macrophage identity and function. Immunity 52:6957–70
    [Google Scholar]
  28. 28. 
    Cox N, Pokrovskii M, Vicario R, Geissmann F. 2021. Origins, biology, and diseases of tissue macrophages. Annu. Rev. Immunol. 39:313–44
    [Google Scholar]
  29. 29. 
    Bharat A, Bhorade SM, Morales-Nebreda L, McQuattie-Pimentel AC, Soberanes S et al. 2016. Flow cytometry reveals similarities between lung macrophages in humans and mice. Am. J. Respir. Cell Mol. Biol. 54:147–49
    [Google Scholar]
  30. 30. 
    Evren E, Ringqvist E, Tripathi KP, Sleiers N, Rives IC et al. 2021. Distinct developmental pathways from blood monocytes generate human lung macrophage diversity. Immunity 54:259–75.e7
    [Google Scholar]
  31. 31. 
    Ruiz-Alcaraz AJ, Carmona-Martinez V, Tristan-Manzano M, Machado-Linde F, Sanchez-Ferrer ML et al. 2018. Characterization of human peritoneal monocyte/macrophage subsets in homeostasis: phenotype, GATA6, phagocytic/oxidative activities and cytokines expression. Sci. Rep. 8:12794
    [Google Scholar]
  32. 32. 
    Bujko A, Atlasy N, Landsverk OJB, Richter L, Yaqub S et al. 2018. Transcriptional and functional profiling defines human small intestinal macrophage subsets. J. Exp. Med. 215:441–58
    [Google Scholar]
  33. 33. 
    Byrne AJ, Powell JE, O'Sullivan BJ, Ogger PP, Hoffland A et al. 2020. Dynamics of human monocytes and airway macrophages during healthy aging and after transplant. J. Exp. Med. 217:e20191236
    [Google Scholar]
  34. 34. 
    MacParland SA, Liu JC, Ma XZ, Innes BT, Bartczak AM et al. 2018. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat. Commun. 9:4383
    [Google Scholar]
  35. 35. 
    Szabo PA, Dogra P, Gray JI, Wells SB, Connors TJ et al. 2021. Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19. Immunity 54:797–814.e6
    [Google Scholar]
  36. 36. 
    Yu YR, Hotten DF, Malakhau Y, Volker E, Ghio AJ et al. 2016. Flow cytometric analysis of myeloid cells in human blood, bronchoalveolar lavage, and lung tissues. Am. J. Respir. Cell Mol. Biol. 54:13–24
    [Google Scholar]
  37. 37. 
    Wu X, Hollingshead N, Roberto J, Knupp A, Kenerson H et al. 2020. Human liver macrophage subsets defined by CD32. Front. Immunol. 11:2108
    [Google Scholar]
  38. 38. 
    MacParland SA, Liu JC, Ma XZ, Innes BT, Bartczak AM et al. 2018. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat. Commun. 9:4383
    [Google Scholar]
  39. 39. 
    Davies LC, Taylor PR. 2015. Tissue-resident macrophages: then and now. Immunology 144:541–48
    [Google Scholar]
  40. 40. 
    Szabo PA, Dogra P, Gray JI, Wells SB, Connors TJ et al. 2021. Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19. Immunity 54:797–814.e6
    [Google Scholar]
  41. 41. 
    Gosselin D, Skola D, Coufal NG, Holtman IR, Schlachetzki JCM et al. 2017. An environment-dependent transcriptional network specifies human microglia identity. Science 356:1248–59
    [Google Scholar]
  42. 42. 
    Hoeffel G, Chen J, Lavin Y, Low D, Almeida FF et al. 2015. c-Myb+ erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42:665–78
    [Google Scholar]
  43. 43. 
    Schmidt SV, Krebs W, Ulas T, Xue J, Babler K et al. 2016. The transcriptional regulator network of human inflammatory macrophages is defined by open chromatin. Cell Res 26:151–70
    [Google Scholar]
  44. 44. 
    Trizzino M, Zucco A, Deliard S, Wang F, Barbieri E et al. 2021. EGR1 is a gatekeeper of inflammatory enhancers in human macrophages. Sci. Adv. 7:eaaz8836
    [Google Scholar]
  45. 45. 
    Bian Z, Gong Y, Huang T, Lee CZW, Bian L et al. 2020. Deciphering human macrophage development at single-cell resolution. Nature 582:571–76
    [Google Scholar]
  46. 46. 
    Rosas M, Davies LC, Giles PJ, Liao CT, Kharfan B et al. 2014. The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal. Science 344:645–48
    [Google Scholar]
  47. 47. 
    Schneider C, Nobs SP, Kurrer M, Rehrauer H, Thiele C, Kopf M 2014. Induction of the nuclear receptor PPAR-γ 3 by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat. Immunol. 15:1026–37
    [Google Scholar]
  48. 48. 
    van de Laar L, Saelens W, De Prijck S, Martens L, Scott CL et al. 2016. Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages. Immunity 44:755–68
    [Google Scholar]
  49. 49. 
    Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A 1999. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 402:34–38
    [Google Scholar]
  50. 50. 
    Gordon CL, Miron M, Thome JJ, Matsuoka N, Weiner J et al. 2017. Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. J. Exp. Med. 214:651–67
    [Google Scholar]
  51. 51. 
    Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P et al. 2013. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity 38:187–97
    [Google Scholar]
  52. 52. 
    Thome JJ, Yudanin N, Ohmura Y, Kubota M, Grinshpun B et al. 2014. Spatial map of human T cell compartmentalization and maintenance over decades of life. Cell 159:814–28
    [Google Scholar]
  53. 53. 
    Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y et al. 2004. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355–60
    [Google Scholar]
  54. 54. 
    Hombrink P, Helbig C, Backer RA, Piet B, Oja AE et al. 2016. Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells. Nat. Immunol. 17:1467–78
    [Google Scholar]
  55. 55. 
    Weinreich MA, Takada K, Skon C, Reiner SL, Jameson SC, Hogquist KA 2009. KLF2 transcription-factor deficiency in T cells results in unrestrained cytokine production and upregulation of bystander chemokine receptors. Immunity 31:122–30
    [Google Scholar]
  56. 56. 
    Klicznik MM, Morawski PA, Höllbacher B, Varkhande SR, Motley SJ et al. 2019. Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy individuals. Sci. Immunol. 4:37eaav8995
    [Google Scholar]
  57. 57. 
    Oja AE, Piet B, Helbig C, Stark R, Van Der Zwan D et al. 2018. Trigger-happy resident memory CD4+ T cells inhabit the human lungs. Mucosal Immunol 11:654–67
    [Google Scholar]
  58. 58. 
    FitzPatrick MEB, Provine NM, Garner LC, Powell K, Amini A et al. 2021. Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets. Cell Rep 34:108661
    [Google Scholar]
  59. 59. 
    Hunter S, Willcox CR, Davey MS, Kasatskaya SA, Jeffery HC et al. 2018. Human liver infiltrating γδ T cells are composed of clonally expanded circulating and tissue-resident populations. J. Hepatol. 69:654–65
    [Google Scholar]
  60. 60. 
    McCully ML, Ladell K, Andrews R, Jones RE, Miners KL et al. 2018. CCR8 expression defines tissue-resident memory T cells in human skin. J. Immunol. 200:1639–50
    [Google Scholar]
  61. 61. 
    Terpstra ML, Remmerswaal EBM, van der Bom-Baylon ND, Sinnige MJ, Kers J et al. 2020. Tissue-resident mucosal-associated invariant T (MAIT) cells in the human kidney represent a functionally distinct subset. Eur. J. Immunol. 50:1783–97
    [Google Scholar]
  62. 62. 
    Kumar BV, Ma W, Miron M, Granot T, Guyer RS et al. 2017. Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep 20:2921–34
    [Google Scholar]
  63. 63. 
    Szabo PA, Levitin HM, Miron M, Snyder ME, Senda T et al. 2019. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease. Nat. Commun. 10:4706
    [Google Scholar]
  64. 64. 
    Cheuk S, Schlums H, Gallais Serezal I, Martini E, Chiang SC et al. 2017. CD49a expression defines tissue-resident CD8+ T cells poised for cytotoxic function in human skin. Immunity 46:287–300
    [Google Scholar]
  65. 65. 
    Miron M, Kumar BV, Meng W, Granot T, Carpenter DJ et al. 2018. Human lymph nodes maintain TCF-1hi memory T cells with high functional potential and clonal diversity throughout life. J. Immunol. 201:2132–40
    [Google Scholar]
  66. 66. 
    Day C, Patel R, Guillen C, Wardlaw AJ. 2009. The chemokine CXCL16 is highly and constitutively expressed by human bronchial epithelial cells. Exp. Lung Res. 35:272–83
    [Google Scholar]
  67. 67. 
    Pallett LJ, Davies J, Colbeck EJ, Robertson F, Hansi N et al. 2017. IL-2high tissue-resident T cells in the human liver: sentinels for hepatotropic infection. J. Exp. Med. 214:1567–80
    [Google Scholar]
  68. 68. 
    Kumar BV, Kratchmarov R, Miron M, Carpenter DJ, Senda T et al. 2018. Functional heterogeneity of human tissue-resident memory T cells based on dye efflux capacities. JCI Insight 3:e123568
    [Google Scholar]
  69. 69. 
    Dogra P, Rancan C, Ma W, Toth M, Senda T et al. 2020. Tissue determinants of human NK cell development, function, and residence. Cell 180:749–63.e13
    [Google Scholar]
  70. 70. 
    Marquardt N, Kekalainen E, Chen P, Lourda M, Wilson JN et al. 2019. Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells. Nat. Commun. 10:3841
    [Google Scholar]
  71. 71. 
    Zhao J, Zhang S, Liu Y, He X, Qu M et al. 2020. Single-cell RNA sequencing reveals the heterogeneity of liver-resident immune cells in human. Cell Discov 6:22
    [Google Scholar]
  72. 72. 
    Brownlie D, Scharenberg M, Mold JE, Hard J, Kekalainen E et al. 2021. Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood. PNAS 118:e2016580118
    [Google Scholar]
  73. 73. 
    Fuchs A, Vermi W, Lee JS, Lonardi S, Gilfillan S et al. 2013. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-gamma-producing cells. Immunity 38:769–81
    [Google Scholar]
  74. 74. 
    Yudanin NA, Schmitz F, Flamar AL, Thome JJC, Tait Wojno E et al. 2019. Spatial and temporal mapping of human innate lymphoid cells reveals elements of tissue specificity. Immunity 50:505–19.e4
    [Google Scholar]
  75. 75. 
    Bar-Ephraim YE, Cornelissen F, Papazian N, Konijn T, Hoogenboezem RM et al. 2017. Cross-tissue transcriptomic analysis of human secondary lymphoid organ-residing ILC3s reveals a quiescent state in the absence of inflammation. Cell Rep 21:823–33
    [Google Scholar]
  76. 76. 
    Bar-Ephraim YE, Koning JJ, Burniol Ruiz E, Konijn T, Mourits VP et al. 2019. CD62L is a functional and phenotypic marker for circulating innate lymphoid cell precursors. J. Immunol. 202:171–82
    [Google Scholar]
  77. 77. 
    Lim AI, Li Y, Lopez-Lastra S, Stadhouders R, Paul F et al. 2017. Systemic human ILC precursors provide a substrate for tissue ILC differentiation. Cell 168:1086–100.e10
    [Google Scholar]
  78. 78. 
    Mjosberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM et al. 2011. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat. Immunol. 12:1055–62
    [Google Scholar]
  79. 79. 
    Simoni Y, Fehlings M, Kloverpris HN, McGovern N, Koo SL et al. 2017. Human innate lymphoid cell subsets possess tissue-type based heterogeneity in phenotype and frequency. Immunity 46:148–61
    [Google Scholar]
  80. 80. 
    Bjorklund AK, Forkel M, Picelli S, Konya V, Theorell J et al. 2016. The heterogeneity of human CD127+ innate lymphoid cells revealed by single-cell RNA sequencing. Nat. Immunol. 17:451–60
    [Google Scholar]
  81. 81. 
    Hoorweg K, Peters CP, Cornelissen F, Aparicio-Domingo P, Papazian N et al. 2012. Functional differences between human NKp44 and NKp44+ RORC+ innate lymphoid cells. Front. Immunol. 3:72
    [Google Scholar]
  82. 82. 
    Ginhoux F, Greter M, Leboeuf M, Nandi S, See P et al. 2010. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–45
    [Google Scholar]
  83. 83. 
    Lavin Y, Mortha A, Rahman A, Merad M. 2015. Regulation of macrophage development and function in peripheral tissues. Nat. Rev. Immunol. 15:731–44
    [Google Scholar]
  84. 84. 
    Gherardini J, Uchida Y, Hardman JA, Chéret J, Mace K et al. 2020. Tissue-resident macrophages can be generated de novo in adult human skin from resident progenitor cells during substance P-mediated neurogenic inflammation ex vivo. PLOS ONE 15:e0227817
    [Google Scholar]
  85. 85. 
    Hsu AP, Sampaio EP, Khan J, Calvo KR, Lemieux JE et al. 2011. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 118:2653–55
    [Google Scholar]
  86. 86. 
    Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF et al. 2010. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115:1519–29
    [Google Scholar]
  87. 87. 
    Eguíluz-Gracia I, Lawaetz Schultz HH, Sikkeland LIB, Danilova E, Holm AM et al. 2016. Long-term persistence of human donor alveolar macrophages in lung transplant recipients. Thorax 71:100611
    [Google Scholar]
  88. 88. 
    Kamada N, Hisamatsu T, Honda H, Kobayashi T, Chinen H et al. 2009. Human CD14+ macrophages in intestinal lamina propria exhibit potent antigen-presenting ability. J. Immunol. 183:1724–31
    [Google Scholar]
  89. 89. 
    Ráki M, Tollefsen S, Molberg Ø, Lundin KEA, Sollid LM, Jahnsen FL. 2006. A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells. Gastroenterology 131:428–38
    [Google Scholar]
  90. 90. 
    Pallett LJ, Burton AR, Amin OE, Rodriguez-Tajes S, Patel AA et al. 2020. Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes. J. Exp. Med. 217:e20200050
    [Google Scholar]
  91. 91. 
    Bajpai G, Schneider C, Wong N, Bredemeyer A, Hulsmans M et al. 2018. The human heart contains distinct macrophage subsets with divergent origins and functions. Nat. Med. 24:1234–45
    [Google Scholar]
  92. 92. 
    McGovern N, Schlitzer A, Gunawan M, Jardine L, Shin A et al. 2014. Human dermal CD14+ cells are a transient population of monocyte-derived macrophages. Immunity 41:465–77
    [Google Scholar]
  93. 93. 
    Wang X, Rao H, Zhao J, Wee A, Li X et al. 2020. STING expression in monocyte-derived macrophages is associated with the progression of liver inflammation and fibrosis in patients with nonalcoholic fatty liver disease. Lab. Investig. 100:542–52
    [Google Scholar]
  94. 94. 
    Jardine L, Cytlak U, Gunawan M, Reynolds G, Green K et al. 2020. Donor monocyte-derived macrophages promote human acute graft-versus-host disease. J. Clin. Investig. 130:4574–86
    [Google Scholar]
  95. 95. 
    Keophiphath M, Rouault C, Divoux A, Clement K, Lacasa D 2010. CCL5 promotes macrophage recruitment and survival in human adipose tissue. Arterioscler. Thromb. Vasc. Biol. 30:39–45
    [Google Scholar]
  96. 96. 
    Goodman T, Lefrancois L. 1989. Intraepithelial lymphocytes: Anatomical site, not T cell receptor form, dictates phenotype and function. J. Exp. Med. 170:1569–81
    [Google Scholar]
  97. 97. 
    Gray EE, Suzuki K, Cyster JG. 2011. Cutting edge: identification of a motile IL-17–producing γδ T cell population in the dermis. J. Immunol. 186:6091–95
    [Google Scholar]
  98. 98. 
    Havran WL, Allison JP. 1990. Origin of Thy-1+ dendritic epidermal cells of adult mice from fetal thymic precursors. Nature 344:68–70
    [Google Scholar]
  99. 99. 
    Itohara S, Farr AG, Lafaille JJ, Bonneville M, Takagaki Y et al. 1990. Homing of a γδ thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. Nature 343:754–57
    [Google Scholar]
  100. 100. 
    Carding SR, Kyes S, Jenkinson EJ, Kingston R, Bottomly K et al. 1990. Developmentally regulated fetal thymic and extrathymic T-cell receptor γδ gene expression. Genes Dev 4:1304–15
    [Google Scholar]
  101. 101. 
    Haas JD, Ravens S, Düber S, Sandrock I, Oberdörfer L et al. 2012. Development of interleukin-17-producing γδ T cells is restricted to a functional embryonic wave. Immunity 37:48–59
    [Google Scholar]
  102. 102. 
    McVay LD, Carding SR. 1996. Extrathymic origin of human gamma delta T cells during fetal development. J. Immunol. 157:72873–82
    [Google Scholar]
  103. 103. 
    McVay LD, Carding SR, Bottomly K, Hayday AC. 1991. Regulated expression and structure of T cell receptor γ/δ transcripts in human thymic ontogeny. EMBO J 10:83–91
    [Google Scholar]
  104. 104. 
    Holtmeier W, Pfänder M, Hennemann A, Zollner TM, Kaufmann R, Caspary WF. 2001. The TCR δ repertoire in normal human skin is restricted and distinct from the TCR δ repertoire in the peripheral blood. J. Investig. Dermatol. 116:275–80
    [Google Scholar]
  105. 105. 
    Toulon A, Breton L, Taylor KR, Tenenhaus M, Bhavsar D et al. 2009. A role for human skin-resident T cells in wound healing. J. Exp. Med. 206:743–50
    [Google Scholar]
  106. 106. 
    Deusch K, Lüling F, Reich K, Classen M, Wagner H, Pfeffer K. 1991. A major fraction of human intraepithelial lymphocytes simultaneously expresses the γ/δ T cell receptor, the CD8 accessory molecule and preferentially uses the Vδ1 gene segment. Eur. J. Immunol. 21:1053–59
    [Google Scholar]
  107. 107. 
    Di Marco Barros R, Roberts NA, Dart RJ, Vantourout P, Jandke A et al. 2016. Epithelia use butyrophilin-like molecules to shape organ-specific γδ T cell compartments. Cell 167:203–18.e17
    [Google Scholar]
  108. 108. 
    Ullrich R, Schieferdecker HL, Ziegler K, Riecken EO, Zeitz M 1990. γδ T cells in the human intestine express surface markers of activation and are preferentially located in the epithelium. Cell. Immunol. 128:619–27
    [Google Scholar]
  109. 109. 
    Stras SF, Werner L, Toothaker JM, Olaloye OO, Oldham AL et al. 2019. Maturation of the human intestinal immune system occurs early in fetal development. Dev. Cell 51:357–73.e5
    [Google Scholar]
  110. 110. 
    Schreurs R, Baumdick ME, Sagebiel AF, Kaufmann M, Mokry M et al. 2019. Human fetal TNF-α-cytokine-producing CD4+ effector memory T cells promote intestinal development and mediate inflammation early in life. Immunity 50:462–76.e8
    [Google Scholar]
  111. 111. 
    Li N, van Unen V, Abdelaal T, Guo N, Kasatskaya SA et al. 2019. Memory CD4+ T cells are generated in the human fetal intestine. Nat. Immunol. 20:301–12
    [Google Scholar]
  112. 112. 
    Thome JJ, Bickham KL, Ohmura Y, Kubota M, Matsuoka N et al. 2016. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues. Nat. Med. 22:72–77
    [Google Scholar]
  113. 113. 
    Senda T, Dogra P, Granot T, Furuhashi K, Snyder ME et al. 2019. Microanatomical dissection of human intestinal T-cell immunity reveals site-specific changes in gut-associated lymphoid tissues over life. Mucosal Immunol 12:378–89
    [Google Scholar]
  114. 114. 
    Connors TJ, Baird JS, Yopes MC, Zens KD, Pethe K et al. 2018. Developmental regulation of effector and resident memory T cell generation during pediatric viral respiratory tract infection. J. Immunol. 201:432–39
    [Google Scholar]
  115. 115. 
    Bourdely P, Anselmi G, Vaivode K, Ramos RN, Missolo-Koussou Y et al. 2020. Transcriptional and functional analysis of CD1c+ human dendritic cells identifies a CD163+ subset priming CD8+CD103+ T cells. Immunity 53:335–52.e8
    [Google Scholar]
  116. 116. 
    Zhang N, Bevan MJ. 2013. Transforming growth factor-beta signaling controls the formation and maintenance of gut-resident memory T cells by regulating migration and retention. Immunity 39:687–96
    [Google Scholar]
  117. 117. 
    Pizzolla A, Nguyen TH, Sant S, Jaffar J, Loudovaris T et al. 2018. Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles. J. Clin. Investig. 128:721–33
    [Google Scholar]
  118. 118. 
    Turner DL, Bickham KL, Thome JJ, Kim CY, D'Ovidio F et al. 2014. Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol 7:501–10
    [Google Scholar]
  119. 119. 
    Poon MML, Byington E, Meng W, Kubota M, Matsumoto R et al. 2021. Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex. Cell Rep 37:9110071
    [Google Scholar]
  120. 120. 
    Poon MML, Rybkina K, Kato Y, Kubota M, Matsumoto R et al. 2021. SARS-CoV-2 infection generates tissue-localized immunological memory in humans. Sci. Immunol 6:65eabl9105
    [Google Scholar]
  121. 121. 
    Hegazy AN, West NR, Stubbington MJT, Wendt E, Suijker KIM et al. 2017. Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 153:1320–37.e16
    [Google Scholar]
  122. 122. 
    Djenidi F, Adam J, Goubar A, Durgeau A, Meurice G et al. 2015. CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients. J. Immunol. 194:3475–86
    [Google Scholar]
  123. 123. 
    Okła K, Farber DL, Zou W. 2021. Tissue-resident memory T cells in tumor immunity and immunotherapy. J. Exp. Med. 218:e20201605
    [Google Scholar]
  124. 124. 
    Matos TR, O'Malley JT, Lowry EL, Hamm D, Kirsch IR et al. 2017. Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones. J. Clin. Investig. 127:4031–41
    [Google Scholar]
  125. 125. 
    Miron M, Meng W, Rosenfeld AM, Dvorkin S, Poon MML et al. 2021. Maintenance of the human memory T cell repertoire by subset and tissue site. Genome Med 13:100
    [Google Scholar]
  126. 126. 
    Morris SE, Farber DL, Yates AJ. 2019. Tissue-resident memory T cells in mice and humans: towards a quantitative ecology. J. Immunol. 203:2561–69
    [Google Scholar]
  127. 127. 
    Snyder ME, Finlayson MO, Connors TJ, Dogra P, Senda T et al. 2019. Generation and persistence of human tissue-resident memory T cells in lung transplantation. Sci. Immunol. 4:eaav5581
    [Google Scholar]
  128. 128. 
    Bartolome-Casado R, Landsverk OJB, Chauhan SK, Richter L, Phung D et al. 2019. Resident memory CD8 T cells persist for years in human small intestine. J. Exp. Med. 216:2412–26
    [Google Scholar]
  129. 129. 
    Bartolomé-Casado R, Landsverk OJB, Chauhan SK, Sætre F, Hagen KT et al. 2021. CD4+ T cells persist for years in the human small intestine and display a TH1 cytokine profile. Mucosal Immunol 14:2402–10
    [Google Scholar]
  130. 130. 
    Zuber J, Shonts B, Lau SP, Obradovic A, Fu J et al. 2016. Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Sci. Immunol. 1:eaah3732
    [Google Scholar]
  131. 131. 
    Hombrink P, Helbig C, Backer RA, Piet B, Oja AE et al. 2016. Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells. Nat. Immunol. 17:1467–78
    [Google Scholar]
  132. 132. 
    Vieira Braga FA, Hertoghs KM, Kragten NA, Doody GM, Barnes NA et al. 2015. Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans. Eur. J. Immunol. 45:2945–58
    [Google Scholar]
  133. 133. 
    Huntington ND, Alves NL, Legrand N, Lim A, Strick-Marchand H et al. 2011. IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo. PNAS 108:6217–22
    [Google Scholar]
  134. 134. 
    Nozad Charoudeh H, Tang Y, Cheng M, Cilio CM, Jacobsen SE, Sitnicka E 2010. Identification of an NK/T cell-restricted progenitor in adult bone marrow contributing to bone marrow- and thymic-dependent NK cells. Blood 116:183–92
    [Google Scholar]
  135. 135. 
    Yu J, Freud AG, Caligiuri MA. 2013. Location and cellular stages of natural killer cell development. Trends Immunol 34:573–82
    [Google Scholar]
  136. 136. 
    Cuff AO, Robertson FP, Stegmann KA, Pallett LJ, Maini MK et al. 2016. Eomeshi NK cells in human liver are long-lived and do not recirculate but can be replenished from the circulation. J. Immunol. 197:4283–91
    [Google Scholar]
  137. 137. 
    Lunemann S, Martrus G, Goebels H, Kautz T, Langeneckert A et al. 2017. Hobit expression by a subset of human liver-resident CD56bright natural killer cells. Sci. Rep. 7:6676
    [Google Scholar]
  138. 138. 
    Melsen JE, Lugthart G, Vervat C, Kielbasa SM, van der Zeeuw SAJ et al. 2018. Human bone marrow-resident natural killer cells have a unique transcriptional profile and resemble resident memory CD8+ T cells. Front. Immunol. 9:1829
    [Google Scholar]
  139. 139. 
    Scoville SD, Mundy-Bosse BL, Zhang MH, Chen L, Zhang X et al. 2016. A progenitor cell expressing transcription factor RORγt generates all human innate lymphoid cell subsets. Immunity 44:1140–50
    [Google Scholar]
  140. 140. 
    Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP et al. 2018. Innate lymphoid cells: 10 years on. Cell 174:1054–66
    [Google Scholar]
  141. 141. 
    Mjosberg J, Bernink J, Golebski K, Karrich JJ, Peters CP et al. 2012. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 37:649–59
    [Google Scholar]
  142. 142. 
    Orecchioni M, Ghosheh Y, Pramod AB, Ley K. 2019. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS−) vs. alternatively activated macrophages. Front. Immunol. 10:1084
    [Google Scholar]
  143. 143. 
    Bissonnette EY, Lauzon-Joset JF, Debley JS, Ziegler SF 2020. Cross-talk between alveolar macrophages and lung epithelial cells is essential to maintain lung homeostasis. Front. Immunol. 11:583042
    [Google Scholar]
  144. 144. 
    Balhara J, Gounni AS. 2012. The alveolar macrophages in asthma: a double-edged sword. Mucosal Immunol 5:605–9
    [Google Scholar]
  145. 145. 
    Berenson CS, Kruzel RL, Eberhardt E, Sethi S 2013. Phagocytic dysfunction of human alveolar macrophages and severity of chronic obstructive pulmonary disease. J. Infect. Dis. 208:2036–45
    [Google Scholar]
  146. 146. 
    Mathias LJ, Khong SML, Spyroglou L, Payne NL, Siatskas C et al. 2013. Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells. J. Immunol. 191:5914–24
    [Google Scholar]
  147. 147. 
    Vlahos R, Bozinovski S. 2014. Role of alveolar macrophages in chronic obstructive pulmonary disease. Front. Immunol. 5:435
    [Google Scholar]
  148. 148. 
    Trapnell BC, Nakata K, Bonella F, Campo I, Griese M et al. 2019. Pulmonary alveolar proteinosis. Nat. Rev. Dis. Primers 5:16
    [Google Scholar]
  149. 149. 
    Bivona JJ, Crymble HM, Guigni BA, Stapleton RD, Files DC et al. 2021. Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS-induced acute lung injury. FASEB J 35:e21462
    [Google Scholar]
  150. 150. 
    Drummond RA, Swamydas M, Oikonomou V, Zhai B, Dambuza IM et al. 2019. CARD9 + microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat. Immunol. 20:559–70
    [Google Scholar]
  151. 151. 
    Larsson BM, Larsson K, Malmberg P, Palmberg L 1999. Gram positive bacteria induce IL-6 and IL-8 production in human alveolar macrophages and epithelial cells. Inflammation 23:217–30
    [Google Scholar]
  152. 152. 
    Bujko A, Atlasy N, Landsverk OJB, Richter L, Yaqub S et al. 2018. Transcriptional and functional profiling defines human small intestinal macrophage subsets. J. Exp. Med. 215:441–58
    [Google Scholar]
  153. 153. 
    Melms JC, Biermann J, Huang H, Wang Y, Nair A et al. 2021. A molecular single-cell lung atlas of lethal COVID-19. Nature 595:114–19
    [Google Scholar]
  154. 154. 
    Arnold CE, Gordon P, Barker RN, Wilson HM. 2015. The activation status of human macrophages presenting antigen determines the efficiency of Th17 responses. Immunobiology 220:10–19
    [Google Scholar]
  155. 155. 
    Muntjewerff EM, Meesters LD, van den Bogaart G. 2020. Antigen cross-presentation by macrophages. Front. Immunol. 11:1276
    [Google Scholar]
  156. 156. 
    Tang-Huau TL, Gueguen P, Goudot C, Durand M, Bohec M et al. 2018. Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway. Nat. Commun. 9:2570
    [Google Scholar]
  157. 157. 
    Dijkgraaf FE, Matos TR, Hoogenboezem M, Toebes M, Vredevoogd DW et al. 2019. Tissue patrol by resident memory CD8+ T cells in human skin. Nat. Immunol. 20:756–64
    [Google Scholar]
  158. 158. 
    Snyder ME, Sembrat J, Noda K, Myerburg MM, Craig A et al. 2021. Human lung-resident macrophages colocalize with and provide costimulation to PD1hi tissue-resident memory T cells. Am. J. Respir. Crit. Care Med. 203:1230–44
    [Google Scholar]
  159. 159. 
    Rao A, Strauss O, Kokkinou E, Bruchard M, Tripathi KP et al. 2020. Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs. Nat. Commun. 11:2049
    [Google Scholar]
  160. 160. 
    Tu Z, Bozorgzadeh A, Pierce RH, Kurtis J, Crispe IN, Orloff MS. 2008. TLR-dependent cross talk between human Kupffer cells and NK cells. J. Exp. Med. 205:233–44
    [Google Scholar]
  161. 161. 
    Pallett LJ, Davies J, Colbeck EJ, Robertson F, Hansi N et al. 2017. IL-2high tissue-resident T cells in the human liver: sentinels for hepatotropic infection. J. Exp. Med. 214:1567–80
    [Google Scholar]
  162. 162. 
    Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A et al. 2016. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection. Nat. Commun. 6:10224 Erratum 2015. Nat. Commun. 7:11011
    [Google Scholar]
  163. 163. 
    Hernández-Castañeda MA, Happ K, Cattalani F, Wallimann A, Blanchard M et al. 2020. γδ T cells kill Plasmodium falciparum in a granzyme- and granulysin-dependent mechanism during the late blood stage. J. Immunol. 204:1798–809
    [Google Scholar]
  164. 164. 
    Couzi L, Pitard V, Sicard X, Garrigue I, Hawchar O et al. 2012. Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa). Blood 119:1418–27
    [Google Scholar]
  165. 165. 
    Li H, Xiang Z, Feng T, Li J, Liu Y et al. 2013. Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells. Cell. Mol. Immunol. 10:159–64
    [Google Scholar]
  166. 166. 
    Vandereyken M, James OJ, Swamy M 2020. Mechanisms of activation of innate-like intraepithelial T lymphocytes. Cell. Immunol. 13:721–31
    [Google Scholar]
  167. 167. 
    Scharenberg M, Vangeti S, Kekalainen E, Bergman P, Al-Ameri M et al. 2019. Influenza A virus infection induces hyperresponsiveness in human lung tissue-resident and peripheral blood NK cells. Front. Immunol. 10:1116
    [Google Scholar]
  168. 168. 
    Blumenthal RL, Campbell DE, Hwang P, DeKruyff RH, Frankel LR, Umetsu DT. 2001. Human alveolar macrophages induce functional inactivation in antigen-specific CD4 T cells. J. Allergy Clin. Immunol. 107:258–64
    [Google Scholar]
  169. 169. 
    Coleman MM, Ruane D, Moran B, Dunne PJ, Keane J, Mills KHG. 2013. Alveolar macrophages contribute to respiratory tolerance by inducing FoxP3 expression in naive T cells. Am. J. Respir. Cell Mol. Biol. 48:773–80
    [Google Scholar]
  170. 170. 
    Grunwell JR, Yeligar SM, Stephenson S, Ping XD, Gauthier TW et al. 2018. TGF-β1 suppresses the type I IFN response and induces mitochondrial dysfunction in alveolar macrophages. J. Immunol. 200:2115–28
    [Google Scholar]
  171. 171. 
    Roth MD, Golub SH. 1993. Human pulmonary macrophages utilize prostaglandins and transforming growth factor β1 to suppress lymphocyte activation. J. Leukoc. Biol. 53:366–71
    [Google Scholar]
  172. 172. 
    Soroosh P, Doherty TA, Duan W, Mehta AK, Choi H et al. 2013. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance. J. Exp. Med. 210:775–88
    [Google Scholar]
  173. 173. 
    Allard B, Panariti A, Martin JG 2018. Alveolar macrophages in the resolution of inflammation, tissue repair, and tolerance to infection. Front. Immunol. 9:1777
    [Google Scholar]
  174. 174. 
    Mahida RY, Scott A, Parekh D, Lugg ST, Hardy RS et al. 2021. Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis. Eur. Respir. J. 58:32100829
    [Google Scholar]
  175. 175. 
    Bajpai G, Schneider C, Wong N, Bredemeyer A, Hulsmans M et al. 2018. The human heart contains distinct macrophage subsets with divergent origins and functions. Nat. Med. 24:1234–45
    [Google Scholar]
  176. 176. 
    Dalby E, Christensen SM, Wang J, Hamidzadeh K, Chandrasekaran P et al. 2020. Immune complex–driven generation of human macrophages with anti-inflammatory and growth-promoting activity. J. Immunol. 205:102–12
    [Google Scholar]
  177. 177. 
    Kasikara C, Schilperoort M, Gerlach B, Xue C, Wang X et al. 2021. Deficiency of macrophage PHACTR1 impairs efferocytosis and promotes atherosclerotic plaque necrosis. J. Clin. Investig. 131:e145275
    [Google Scholar]
  178. 178. 
    Soares L, Tsavaler L, Rivas A, Engleman E. 1998. V7 (CD101) ligation inhibits TCR/CD3-induced IL-2 production by blocking Ca2+ flux and nuclear factor of activated T cell nuclear translocation. J. Immunol. 161:209–17
    [Google Scholar]
  179. 179. 
    Smolders J, Heutinck KM, Fransen NL, Remmerswaal EBM, Hombrink P et al. 2018. Tissue-resident memory T cells populate the human brain. Nat. Commun. 9:14593
    [Google Scholar]
  180. 180. 
    Watad A, Rowe H, Russell T, Zhou Q, Anderson LK et al. 2020. Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression. Ann. Rheumat. Dis. 79:1044–54
    [Google Scholar]
  181. 181. 
    Lam AJ, MacDonald KN, Pesenacker AM, Juvet SC, Morishita KA et al. 2019. Innate control of tissue-reparative human regulatory T cells. J. Immunol. 202:2195–209
    [Google Scholar]
  182. 182. 
    Casetti R, Agrati C, Wallace M, Sacchi A, Martini F et al. 2009. Cutting edge: TGF-β1 and IL-15 induce FOXP3 + γδ regulatory T cells in the presence of antigen stimulation. J. Immunol. 183:3574–77
    [Google Scholar]
  183. 183. 
    Kouakanou L, Peters C, Sun Q, Floess S, Bhat J et al. 2020. Vitamin C supports conversion of human γδ T cells into FOXP3-expressing regulatory cells by epigenetic regulation. Sci. Rep. 10:6550
    [Google Scholar]
  184. 184. 
    Kühl AA, Pawlowski NN, Grollich K, Blessenohl M, Westermann J et al. 2009. Human peripheral γδ T cells possess regulatory potential. Immunology 128:580–88
    [Google Scholar]
  185. 185. 
    Krishnan S, Prise IE, Wemyss K, Schenck LP, Bridgeman HM et al. 2018. Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis. PNAS 115:10738–43
    [Google Scholar]
  186. 186. 
    Fazio J, Quabius ES, Müller A, Adam-Klages S, Wesch D et al. 2013. Vδ2 T cell deficiency in granulomatosis with polyangiitis (Wegener's granulomatosis). Clin. Immunol. 149:65–72
    [Google Scholar]
  187. 187. 
    Cerboni C, Zingoni A, Cippitelli M, Piccoli M, Frati L, Santoni A 2007. Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK- cell lysis. Blood 110:606–15
    [Google Scholar]
  188. 188. 
    Rabinovich BA, Li J, Shannon J, Hurren R, Chalupny J et al. 2003. Activated, but not resting, T cells can be recognized and killed by syngeneic NK cells. J. Immunol. 170:3572–6
    [Google Scholar]
  189. 189. 
    Nielsen N, Odum N, Urso B, Lanier LL, Spee P. 2012. Cytotoxicity of CD56bright NK cells towards autologous activated CD4+ T cells is mediated through NKG2D, LFA-1 and TRAIL and dampened via CD94/NKG2A. PLOS ONE 7:e31959
    [Google Scholar]
  190. 190. 
    Fasbender F, Widera A, Hengstler JG, Watzl C. 2016. Natural killer cells and liver fibrosis. Front. Immunol. 7:19
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-093019-112809
Loading
/content/journals/10.1146/annurev-immunol-093019-112809
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