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Crosstalk between γδ T cells and the microbiota

Abstract

The role of the microbiota in the development and function of γδ T cells—a T cell subset characterized by a T cell receptor composed of one γ-chain and one δ-chain—has been investigated in multiple organs in mice and humans. Interactions between the microbiota and γδ T cells affect both tissue homeostasis and disease pathologies. Notably, microbiota-induced interleukin-17 (IL-17)-producing-γδ T cells can mediate a range of immunological processes, from metabolic disorders to neuroinflammation via the gut–brain axis. However, the bidirectional interactions between γδ T cells and the microbiota have not been fully determined. In this Perspective, we dissect the roles of microbiota in modulating γδ T cell development and function, and evaluate the evidence for γδ T cell selection of commensal communities. We also discuss the potential implications of these cells in health and disease and the major open questions and research avenues in the field.

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Fig. 1: Microbiota–γδ T cell crosstalk in the skin.
Fig. 2: Microbiota-mediated control of γδ17 T cells and their impact on liver and brain inflammation.

References

  1. 1.

    Ribot, J. C., Lopes, N. & Silva-Santos, B. γδ T cells in tissue physiology and surveillance. Nat. Rev. Immunol. 21, 221–232 (2021).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Willcox, B. E. & Willcox, C. R. γδ TCR ligands: the quest to solve a 500-million-year-old mystery. Nat. Immunol. 20, 121–128 (2019).

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Silva-Santos, B., Mensurado, S. & Coffelt, S. B. γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer. Nat. Rev. Cancer 19, 392–404 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  4. 4.

    Khairallah, C. et al. γδ T cells confer protection against murine cytomegalovirus (MCMV). PLoS Pathog. 11, e1004702 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  5. 5.

    Agrati, C. et al. Activation of Vγ9Vδ2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication. Int. Immunol. 18, 11–18 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  6. 6.

    Boullier, S., Dadaglio, G., Lafeuillade, A., Debord, T. & Gougeon, M. L. V delta 1 T cells expanded in the blood throughout HIV infection display a cytotoxic activity and are primed for TNF-alpha and IFN-gamma production but are not selected in lymph nodes. J. Immunol. 159, 3629–3637 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Couzi, L. et al. Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa). Blood 119, 1418–1427 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Kodukula, P., Liu, T., Rooijen, N. V., Jager, M. J. & Hendricks, R. L. Macrophage control of herpes simplex virus type 1 replication in the peripheral nervous system. J. Immunol. 162, 2895–2905 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Poccia, F. et al. Anti-severe acute respiratory syndrome coronavirus immune responses: the role played by Vγ9Vδ2 T cells. J. Infect. Dis. 193, 1244–1249 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Selin, L. K., Santolucito, P. A., Pinto, A. K., Szomolanyi-Tsuda, E. & Welsh, R. M. Innate immunity to viruses: control of vaccinia virus infection by γδ T cells. J. Immunol. 166, 6784–6794 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Tsai, C. Y. et al. Type I IFNs and IL-18 regulate the antiviral response of primary human γδ T cells against dendritic cells infected with Dengue virus. J. Immunol. 194, 3890–3900 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  12. 12.

    Xiang, Z. et al. Targeted activation of human Vγ9Vδ2-T cells controls epstein-barr virus-induced B cell lymphoproliferative disease. Cancer Cell 26, 565–576 (2014).

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Fiala, G. J., Gomes, A. Q. & Silva-Santos, B. From thymus to periphery: molecular basis of effector γδ-T cell differentiation. Immunol. Rev. 298, 47–60 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Bandeira, A. et al. Localization of gamma/delta T cells to the intestinal epithelium is independent of normal microbial colonization. J. Exp. Med. 172, 239–244 (1990).

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Di Marco Barros, R. et al. Epithelia use butyrophilin-like molecules to shape organ-specific γδ T cell compartments. Cell 167, 203–218 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Li, F. et al. The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner. Nat. Commun. 7, 13839 (2017).

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Duan, J., Chung, H., Troy, E. & Kasper, D. L. Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing γ/δ T cells. Cell Host Microbe 7, 140–150 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Prinz, I., Silva-Santos, B. & Pennington, D. J. Functional development of γδ T cells. Eur. J. Immunol. 43, 1988–1994 (2013).

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Carding, S. R. & Egan, P. J. γδ T cells: functional plasticity and heterogeneity. Nat. Rev. Immunol. 2, 336–345 (2002).

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Li, Y. et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147, 629–640 (2011).

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Ivanov, I. I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Benakis, C. et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat. Med. 22, 516–523 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Chodaczek, G., Papanna, V., Zal, M. A. & Zal, T. Body-barrier surveillance by epidermal γδ TCRs. Nat. Immunol. 13, 272–282 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Wilharm, A. et al. Mutual interplay between IL-17-producing γδT cells and microbiota orchestrates oral mucosal homeostasis. Proc. Natl Acad. Sci. USA 116, 2652–2661 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Ridaura, V. K. et al. Contextual control of skin immunity and inflammation by Corynebacterium. J. Exp. Med. 215, 785–799 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    St Leger, A. J. et al. An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal γδ T cells. Immunity 47, 148–158 (2017).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  28. 28.

    Papotto, P. H. et al. IL-23 drives differentiation of peripheral γδ17 T cells from adult bone marrow-derived precursors. EMBO Rep. 18, 1957–1967 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    Lai, Y. et al. Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections. J. Invest. Dermatol. 130, 2211–2221 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Lai, Y. et al. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nat. Med. 15, 1377–1382 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Ribeiro, M. et al. Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory. Sci. Immunol. 4, eaay5199 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Alves de Lima, K. et al. Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons. Nat. Immunol. 21, 1421–1429 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Monin, L. et al. γδ T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis. Mucosal Immunol. 13, 969–981 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Krishnan, S. et al. Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis. Proc. Natl Acad. Sci. USA 115, 10738–10743 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Wilharm, A. et al. Microbiota-dependent expansion of testicular IL-17-producing Vγ6+ γδ T cells upon puberty promotes local tissue immune surveillance. Mucosal Immmunol. 14, 242–252 (2020).

    Article  CAS  Google Scholar 

  36. 36.

    Tedesco, D. et al. Alterations in intestinal microbiota lead to production of interleukin 17 by intrahepatic γδ T-cell receptor-positive cells and pathogenesis of cholestatic liver disease. Gastroenterology 154, 2178–2193 (2018).

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Jin, C. et al. Commensal microbiota promote lung cancer development via γδ T cells. Cell 176, 998–1013 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Tan, L. et al. Single-cell transcriptomics identifies the adaptation of Scart1+ Vγ6+ T cells to skin residency as activated effector cells. Cell Rep. 27, 3657–3671 e3654 (2019).

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  40. 40.

    Muller, P. A. et al. Microbiota modulate sympathetic neurons via a gut–brain circuit. Nature 583, 441–446 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Chang, C. S. & Kao, C. Y. Current understanding of the gut microbiota shaping mechanisms. J. Biomed. Sci. 26, 59 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. 42.

    Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res. 30, 492–506 (2020).

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Koren, N. et al. Maturation of the neonatal oral mucosa involves unique epithelium–microbiota interactions. Cell Host Microbe 29, 197–209 (2020).

    Article  CAS  Google Scholar 

  44. 44.

    Kumar, P. et al. Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation. Immunity 44, 659–671 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Floudas, A. et al. IL-17 receptor A maintains and protects the skin barrier to prevent allergic skin inflammation. J. Immunol. 199, 707–717 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Regen, T. et al. IL-17 controls central nervous system autoimmunity through the intestinal microbiome. Sci. Immunol. 6, eaaz6563 (2021).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. 47.

    Gregor, M. F. & Hotamisligil, G. S. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 29, 415–445 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  49. 49.

    Cani, P. D. et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 1470–1481 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  50. 50.

    Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

    PubMed  Article  PubMed Central  Google Scholar 

  51. 51.

    Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  52. 52.

    Garidou, L. et al. The gut microbiota regulates intestinal CD4 T cells expressing RORgammat and controls metabolic disease. Cell Metab. 22, 100–112 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  53. 53.

    Amar, J. et al. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol. Med. 3, 559–572 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Monteiro-Sepulveda, M. et al. Jejunal T cell inflammation in human obesity correlates with decreased enterocyte insulin signaling. Cell Metab. 22, 113–124 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  55. 55.

    Costanzo, A. E. et al. Obesity impairs γδ T cell homeostasis and antiviral function in humans. PLoS ONE 10, e0120918 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  56. 56.

    Bisanz, J. E., Upadhyay, V., Turnbaugh, J. A., Ly, K. & Turnbaugh, P. J. Meta-analysis reveals reproducible gut microbiome alterations in response to a high-fat diet. Cell Host Microbe 26, 265–272 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Caspar-Bauguil, S. et al. Adipose tissues as an ancestral immune organ: site-specific change in obesity. FEBS Lett. 579, 3487–3492 (2005).

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Mehta, P., Nuotio-Antar, A. M. & Smith, C. W. γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice. J. Leukoc. Biol. 97, 121–134 (2015).

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Luck, H. et al. Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metab. 21, 527–542 (2015).

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Craven, L. et al. Allogenic fecal microbiota transplantation in patients with nonalcoholic fatty liver disease improves abnormal small intestinal permeability: a randomized control trial. Am. J. Gastroenterol. 115, 1055–1065 (2020).

    PubMed  Article  Google Scholar 

  61. 61.

    Mouzaki, M. et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58, 120–127 (2013).

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Del Chierico, F. et al. Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology 65, 451–464 (2017).

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    Loomba, R. et al. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab. 25, 1054–1062 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. 64.

    Torres-Hernandez, A. et al. γδ T cells promote steatohepatitis by orchestrating innate and adaptive immune programming. Hepatology 71, 477–494 (2020).

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Zhou, D. et al. Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci. Rep. 7, 1529 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  66. 66.

    Cryan, J. F. et al. The microbiota–gut–brain axis. Physiol. Rev. 99, 1877–2013 (2019).

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Morais, L. H., Schreiber, H. L. T. & Mazmanian, S. K. The gut microbiota–brain axis in behaviour and brain disorders. Nat. Rev. Microbiol. 19, 241–255 (2020).

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Shichita, T. et al. Pivotal role of cerebral interleukin-17-producing γδT cells in the delayed phase of ischemic brain injury. Nat. Med. 15, 946–950 (2009).

    CAS  PubMed  Article  Google Scholar 

  69. 69.

    Arunachalam, P. et al. CCR6 (CC chemokine receptor 6) is essential for the migration of detrimental natural interleukin-17-producing γδ T cells in stroke. Stroke 48, 1957–1965 (2017).

    CAS  PubMed  Article  Google Scholar 

  70. 70.

    Papotto, P. H., Reinhardt, A., Prinz, I. & Silva-Santos, B. Innately versatile: γδ17 T cells in inflammatory and autoimmune diseases. J. Autoimmun. 87, 26–37 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  71. 71.

    Sutton, C. E. et al. Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity 31, 331–341 (2009).

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Petermann, F. et al. gammadelta T cells enhance autoimmunity by restraining regulatory T cell responses via an interleukin-23-dependent mechanism. Immunity 33, 351–363 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    Berer, K. et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538–541 (2011).

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Lee, Y. K., Menezes, J. S., Umesaki, Y. & Mazmanian, S. K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA 108, 4615–4622 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    Ericsson, A. C. et al. The influence of caging, bedding, and diet on the composition of the microbiota in different regions of the mouse gut. Sci. Rep. 8, 4065 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  76. 76.

    McCoy, K. D., Geuking, M. B. & Ronchi, F. Gut microbiome standardization in control and experimental mice. Curr. Protoc. Immunol. 117, 23.1.1–23.1.13 (2017).

    Article  Google Scholar 

  77. 77.

    Chang, P. V., Hao, L., Offermanns, S. & Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl Acad. Sci. USA 111, 2247–2252 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Kelly, C. J. et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17, 662–671 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 79.

    Becattini, S. et al. Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation. Cell Host Microbe 29, 378–393 (2021).

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Sheridan, B. S. & Lefrancois, L. Intraepithelial lymphocytes: to serve and protect. Curr. Gastroenterol. Rep. 12, 513–521 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. 82.

    Viladomiu, M. et al. IgA-coated E. coli enriched in Crohn’s disease spondyloarthritis promote TH17-dependent inflammation. Sci. Transl. Med. 9, eaaf9655 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  83. 83.

    Zielinski, C. E. et al. Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature 484, 514–518 (2012).

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Lin, L. et al. Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice. PLoS Pathog. 5, e1000703 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  85. 85.

    Tan, T. G. et al. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. Proc. Natl Acad. Sci. USA 113, E8141–E8150 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    Hernandez-Santos, N. et al. Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections. Mucosal Immunol. 6, 900–910 (2013).

    CAS  PubMed  Article  Google Scholar 

  87. 87.

    Hernandez-Santos, N. & Gaffen, S. L. Th17 cells in immunity to Candida albicans. Cell Host Microbe 11, 425–435 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. 88.

    Round, J. L. et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332, 974–977 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  89. 89.

    Chiba, T. & Seno, H. Indigenous clostridium species regulate systemic immune responses by induction of colonic regulatory T cells. Gastroenterology 141, 1114–1116 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  90. 90.

    Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    Yilmaz, B. et al. Microbial network disturbances in relapsing refractory Crohn’s disease. Nat. Med. 25, 323–336 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  92. 92.

    Hang, S. et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature 576, 143–148 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. 93.

    Wen, L. et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455, 1109–1113 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  94. 94.

    Wang, S. et al. MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity 43, 289–303 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  95. 95.

    Ehmann, D. et al. Paneth cell alpha-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments. Proc. Natl Acad. Sci. USA 116, 3746–3751 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  96. 96.

    Flo, T. H. et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432, 917–921 (2004).

    CAS  PubMed  Article  Google Scholar 

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Acknowledgements

We thank J. C. Ribot for insightful discussions on this topic. Figures were created with BioRender.com. Our work is supported by European Molecular Biology Organization (LTF 191-2019) to P.H.P., Swiss National Foundation (SNF) Ambizione Grant PZ00P3_185880 and Novartis Foundation for Medical-Biological Research (no. 19A013) to B.Y., and ‘la Caixa’ Foundation (ID 100010434, LCF/PR/HR19/52160011) to B.S.-S.

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P.H.P. and B.Y. drafted the manuscript and prepared the figures. B.S.-S. critically revised and finalized the manuscript.

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Correspondence to Pedro H. Papotto or Bruno Silva-Santos.

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Papotto, P.H., Yilmaz, B. & Silva-Santos, B. Crosstalk between γδ T cells and the microbiota. Nat Microbiol 6, 1110–1117 (2021). https://doi.org/10.1038/s41564-021-00948-2

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