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Group 3 innate lymphoid cells in intestinal health and disease

Nature Reviews Gastroenterology & Hepatology volume 21, pages 428–443 (2024)Cite this article

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Abstract

The gastrointestinal tract is an immunologically rich organ, containing complex cell networks and dense lymphoid structures that safeguard this large absorptive barrier from pathogens, contribute to tissue physiology and support mucosal healing. Simultaneously, the immune system must remain tolerant to innocuous dietary antigens and trillions of normally beneficial microorganisms colonizing the intestine. Indeed, a dysfunctional immune response in the intestine underlies the pathogenesis of numerous local and systemic diseases, including inflammatory bowel disease, food allergy, chronic enteric infections or cancers. Here, we discuss group 3 innate lymphoid cells (ILC3s), which have emerged as orchestrators of tissue physiology, immunity, inflammation, tolerance and malignancy in the gastrointestinal tract. ILC3s are abundant in the developing and healthy intestine but their numbers or function are altered during chronic disease and cancer. The latest studies provide new insights into the mechanisms by which ILC3s fundamentally shape intestinal homeostasis or disease pathophysiology, and often this functional dichotomy depends on context and complex interactions with other cell types or microorganisms. Finally, we consider how this knowledge could be harnessed to improve current treatments or provoke new opportunities for therapeutic intervention to promote gut health.

Key points

  • Group 3 innate lymphoid cells (ILC3s) have emerged as critical orchestrators of intestinal health and disease.

  • At homeostasis, ILC3s instruct lymphoid tissue organogenesis and persist throughout life to protect from enteric pathogens whilst supporting barrier integrity and tolerance towards microbiota and dietary antigens.

  • A balance between ILC3s and adaptive immune responses is essential to protect from enteric pathogens and promote immune regulation, whereas disruption of ILC3s unleashes chronic gut inflammation.

  • Dysregulation of ILC3s also contributes to experimental intestinal inflammation and cancer but critically depends on contextual factors such as the presence of adaptive immunity and disease timepoint.

  • Gut-protective ILC3s are dramatically reduced in both inflammatory bowel disease and colorectal cancer, whereas the remaining cells show increased plasticity towards inflammatory phenotypes.

  • Modulating ILC3 numbers or function could considerably improve gastrointestinal health by limiting inflammation, promoting mucosal healing or supporting antitumour responses.

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Fig. 1: Phenotype and spatiotemporal properties of ILC3 subsets in the human and mouse intestine.
Fig. 2: ILC3s orchestrate tissue physiology and immune tolerance in the gut.
Fig. 3: ILC3s in human IBD and CRC.
Fig. 4: Harnessing ILC3s as a novel therapy to promote gut health.

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References

  1. Spits, H. et al. Innate lymphoid cells — a proposal for uniform nomenclature. Nat. Rev. Immunol. 13, 145–149 (2013).

    CAS  PubMed  Google Scholar 

  2. Sonnenberg, G. F. & Artis, D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat. Med. 21, 698–708 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Vivier, E. et al. Innate lymphoid cells: 10 years on. Cell 174, 1054–1066 (2018).

    CAS  PubMed  Google Scholar 

  4. Cella, M. et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457, 722–725 (2009).

    CAS  PubMed  Google Scholar 

  5. Satoh-Takayama, N. et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29, 958–970 (2008).

    CAS  PubMed  Google Scholar 

  6. Sanos, S. L. et al. RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat. Immunol. 10, 83–91 (2009).

    CAS  PubMed  Google Scholar 

  7. Luci, C. et al. Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin. Nat. Immunol. 10, 75–82 (2009).

    CAS  PubMed  Google Scholar 

  8. Satoh-Takayama, N. et al. IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors. J. Exp. Med. 207, 273–280 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Crellin, N. K., Trifari, S., Kaplan, C. D., Cupedo, T. & Spits, H. Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells. J. Exp. Med. 207, 281–290 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Klose, C. S. N. et al. A T-bet gradient controls the fate and function of CCR6–RORγt+ innate lymphoid cells. Nature 494, 261–265 (2013).

    CAS  PubMed  Google Scholar 

  11. Reynders, A. et al. Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt– lymphoid cells. EMBO J. 30, 2934–2947 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Hernández, P. P. et al. Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection. Nat. Immunol. 16, 698–707 (2015).

    PubMed  PubMed Central  Google Scholar 

  13. Vonarbourg, C. et al. Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt+ innate lymphocytes. Immunity 33, 736–751 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Bernink, J. H. et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat. Immunol. 14, 221–229 (2013).

    CAS  PubMed  Google Scholar 

  15. Mebius, R. E., Rennert, P. & Weissman, I. L. Developing lymph nodes collect CD4+CD3– LTβ+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity 7, 493–504 (1997).

    CAS  PubMed  Google Scholar 

  16. Eberl, G. et al. An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells. Nat. Immunol. 5, 64–73 (2004).

    CAS  PubMed  Google Scholar 

  17. Eberl, G. & Littman, D. R. Thymic origin of intestinal αβ T cells revealed by fate mapping of RORγt+ cells. Science 305, 248–251 (2004).

    CAS  PubMed  Google Scholar 

  18. Cupedo, T. et al. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat. Immunol. 10, 66–74 (2009).

    CAS  PubMed  Google Scholar 

  19. Sawa, S. et al. Lineage relationship analysis of RORγt+ innate lymphoid cells. Science 330, 665–669 (2010).

    CAS  PubMed  Google Scholar 

  20. Gladiator, A., Wangler, N., Trautwein-Weidner, K. & LeibundGut-Landmann, S. Cutting edge: IL-17-secreting innate lymphoid cells are essential for host defense against fungal infection. J. Immunol. 190, 521–525 (2013).

    CAS  PubMed  Google Scholar 

  21. Sonnenberg, G. F., Monticelli, L. A., Elloso, M. M., Fouser, L. A. & Artis, D. CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34, 122–134 (2011).

    CAS  PubMed  Google Scholar 

  22. Buonocore, S. et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464, 1371–1375 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Grigg, J. B. et al. Antigen-presenting innate lymphoid cells orchestrate neuroinflammation. Nature 600, 707–712 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Cording, S. et al. Mouse models for the study of fate and function of innate lymphoid cells. Eur. J. Immunol. 48, 1271–1280 (2018).

    CAS  PubMed  Google Scholar 

  25. Jarick, K. J. et al. Non-redundant functions of group 2 innate lymphoid cells. Nature 611, 794–800 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Tsou, A. M. et al. Neuropeptide regulation of non-redundant ILC2 responses at barrier surfaces. Nature 611, 787–793 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Mjösberg, J. & Spits, H. Human innate lymphoid cells. J. Allergy Clin. Immunol. 138, 1265–1276 (2016).

    PubMed  Google Scholar 

  28. Bal, S. M., Golebski, K. & Spits, H. Plasticity of innate lymphoid cell subsets. Nat. Rev. Immunol. 20, 552–565 (2020).

    CAS  PubMed  Google Scholar 

  29. Glatzer, T. et al. RORγt+ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44. Immunity 38, 1223–1235 (2013).

    CAS  PubMed  Google Scholar 

  30. Shikhagaie, M. M. et al. Neuropilin-1 is expressed on lymphoid tissue residing LTi-like group 3 innate lymphoid cells and associated with ectopic lymphoid aggregates. Cell Rep. 18, 1761–1773 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Björklund, Å. K. et al. The heterogeneity of human CD127+ innate lymphoid cells revealed by single-cell RNA sequencing. Nat. Immunol. 17, 451–460 (2016).

    PubMed  Google Scholar 

  32. Mazzurana, L. et al. Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing. Cell Res. 31, 554–568 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Montaldo, E., Juelke, K. & Romagnani, C. Group 3 innate lymphoid cells (ILC3s): origin, differentiation, and plasticity in humans and mice. Eur. J. Immunol. 45, 2171–2182 (2015).

    CAS  PubMed  Google Scholar 

  34. Klose, C. S. N. et al. Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157, 340–356 (2014).

    CAS  PubMed  Google Scholar 

  35. Cherrier, M., Sawa, S. & Eberl, G. Notch, Id2, and RORγt sequentially orchestrate the fetal development of lymphoid tissue inducer cells. J. Exp. Med. 209, 729–740 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Constantinides, M. G., McDonald, B. D., Verhoef, P. A. & Bendelac, A. A committed precursor to innate lymphoid cells. Nature 508, 397–401 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Montaldo, E. et al. Human RORγt+ CD34+ cells are lineage-specified progenitors of group 3 RORγt+ innate lymphoid cells. Immunity 41, 988–1000 (2014).

    CAS  PubMed  Google Scholar 

  38. Hernández, D. C. et al. An in vitro platform supports generation of human innate lymphoid cells from CD34+ hematopoietic progenitors that recapitulate ex vivo identity. Immunity 54, 2417–2432.e5 (2021).

    PubMed  Google Scholar 

  39. Lim, A. I. et al. Systemic human ILC precursors provide a substrate for tissue ILC differentiation. Cell 168, 1086–1100.e10 (2017).

    CAS  PubMed  Google Scholar 

  40. Jowett, G. M. et al. Organoids capture tissue-specific innate lymphoid cell development in mice and humans. Cell Rep. 40, 111281 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Possot, C. et al. Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells. Nat. Immunol. 12, 949–958 (2011).

    CAS  PubMed  Google Scholar 

  42. Yudanin, N. A. et al. Spatial and temporal mapping of human innate lymphoid cells reveals elements of tissue specificity. Immunity 50, 505–519.e4 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Krämer, B. et al. Compartment-specific distribution of human intestinal innate lymphoid cells is altered in HIV patients under effective therapy. PLoS Pathog. 13, e1006373 (2017).

    PubMed  PubMed Central  Google Scholar 

  44. Elmentaite, R. et al. Cells of the human intestinal tract mapped across space and time. Nature 597, 250–255 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Fawkner-Corbett, D. et al. Spatiotemporal analysis of human intestinal development at single-cell resolution. Cell 184, 810–826.e23 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Shen, X. et al. Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging. Nat. Aging 3, 965–981 (2023).

    CAS  PubMed  Google Scholar 

  47. Kanamori, Y. et al. Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+IL-7R+Thy1+ lympho-hemopoietic progenitors develop. J. Exp. Med. 184, 1449–1459 (1996).

    CAS  PubMed  Google Scholar 

  48. Hamada, H. et al. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J. Immunol. 168, 57–64 (2002).

    CAS  PubMed  Google Scholar 

  49. Kiss, E. A. et al. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334, 1561–1565 (2011).

    CAS  PubMed  Google Scholar 

  50. Qiu, J. et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36, 92–104 (2012).

    CAS  PubMed  Google Scholar 

  51. Li, S. et al. Aryl hydrocarbon receptor signaling cell intrinsically inhibits intestinal group 2 innate lymphoid cell function. Immunity 49, 915–928.e5 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Spencer, S. P. et al. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science 343, 432–437 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Lin, Y.-D., Arora, J., Diehl, K., Bora, S. A. & Cantorna, M. T. Vitamin D is required for ILC3 derived IL-22 and protection from Citrobacter rodentium infection. Front. Immunol. 10, 1 (2019).

    PubMed  PubMed Central  Google Scholar 

  54. van de Pavert, S. A. et al. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity. Nature 508, 123–127 (2014).

    PubMed  PubMed Central  Google Scholar 

  55. Mielke, L. A. et al. Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation. J. Exp. Med. 210, 1117–1124 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Hooper, L. V., Midtvedt, T. & Gordon, J. I. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu. Rev. Nutr. 22, 283–307 (2002).

    CAS  PubMed  Google Scholar 

  57. Cheng, H.-W. et al. Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function. Nat. Commun. 13, 2027 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Longman, R. S. et al. CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. J. Exp. Med. 211, 1571–1583 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Castellanos, J. G. et al. Microbiota-induced TNF-like ligand 1A drives group 3 innate lymphoid cell-mediated barrier protection and intestinal T cell activation during colitis. Immunity 49, 1077–1089.e5 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Mortha, A. et al. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343, 1249288 (2014).

    PubMed  PubMed Central  Google Scholar 

  61. Guendel, F. et al. Group 3 innate lymphoid cells program a distinct subset of IL-22BP-producing dendritic cells demarcating solitary intestinal lymphoid tissues. Immunity 53, 1015–1032.e8 (2020).

    CAS  PubMed  Google Scholar 

  62. Yano, H. & Artis, D. Neuronal regulation of innate lymphoid cell responses. Curr. Opin. Immunol. 76, 102205 (2022).

    CAS  PubMed  Google Scholar 

  63. Dalli, J., Colas, R. A., Arnardottir, H. & Serhan, C. N. Vagal regulation of group 3 innate lymphoid cells and the immunoresolvent PCTR1 controls infection resolution. Immunity 46, 92–105 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Ibiza, S. et al. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature 535, 440–443 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Wang, P. et al. Adrenergic nerves regulate intestinal regeneration through IL-22 signaling from type 3 innate lymphoid cells. Cell Stem Cell 30, 1166–1178.e8 (2023).

    CAS  PubMed  Google Scholar 

  66. Talbot, J. et al. Feeding-dependent VIP neuron-ILC3 circuit regulates the intestinal barrier. Nature 579, 575–580 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Seillet, C. et al. The neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity. Nat. Immunol. 21, 168–177 (2020).

    CAS  PubMed  Google Scholar 

  68. Yu, H. B. et al. Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells. Proc. Natl Acad. Sci. USA 118, e2016634118 (2021).

    Google Scholar 

  69. Pascal, M. et al. The neuropeptide VIP potentiates intestinal innate type 2 and type 3 immunity in response to feeding. Mucosal Immunol. 15, 629–641 (2022).

    CAS  PubMed  Google Scholar 

  70. Wang, Q. et al. Circadian rhythm-dependent and circadian rhythm-independent impacts of the molecular clock on type 3 innate lymphoid cells. Sci. Immunol. 4, eaay7501 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Godinho-Silva, C. et al. Light-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis. Nature 574, 254–258 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Teng, F. et al. A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut. Sci. Immunol. 4, eaax1215 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Nussbaum, J. C. et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502, 245–248 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Thaiss, C. A. et al. Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167, 1495–1510.e12 (2016).

    CAS  PubMed  Google Scholar 

  75. Cella, M., Otero, K. & Colonna, M. Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity. Proc. Natl Acad. Sci. USA 107, 10961–10966 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Cella, M. et al. Subsets of ILC3-ILC1-like cells generate a diversity spectrum of innate lymphoid cells in human mucosal tissues. Nat. Immunol. 20, 980–991 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Bernink, J. H. et al. Interleukin-12 and -23 control plasticity of CD127+ group 1 and group 3 innate lymphoid cells in the intestinal lamina propria. Immunity 43, 146–160 (2015).

    CAS  PubMed  Google Scholar 

  78. Pokrovskii, M. et al. Characterization of transcriptional regulatory networks that promote and restrict identities and functions of intestinal innate lymphoid cells. Immunity 51, 185–197.e6 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Tizian, C. et al. c-Maf restrains T-bet-driven programming of CCR6-negative group 3 innate lymphoid cells. eLife 9, e52549 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Goc, J. et al. Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer. Cell 184, 5015–5030.e16 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Kokkinou, E. et al. CD45RA+CD62L– ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs. Sci. Immunol. 7, eabj8301 (2022).

    CAS  PubMed  Google Scholar 

  82. Kokkinou, E. et al. The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis. Cell Rep. Med. 4, 101038 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Gasteiger, G., Fan, X., Dikiy, S., Lee, S. Y. & Rudensky, A. Y. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science 350, 981–985 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Huang, Y. et al. S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense. Science 359, 114–119 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Emgård, J. et al. Oxysterol sensing through the receptor GPR183 promotes the lymphoid-tissue-inducing function of innate lymphoid cells and colonic inflammation. Immunity 48, 120–132.e8 (2018).

    PubMed  PubMed Central  Google Scholar 

  86. Pearson, C. et al. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation. eLife 5, e10066 (2016).

    PubMed  PubMed Central  Google Scholar 

  87. Jarade, A. et al. Inflammation triggers ILC3 patrolling of the intestinal barrier. Nat. Immunol. 23, 1317–1323 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Mackley, E. C. et al. CCR7-dependent trafficking of RORγ+ ILCs creates a unique microenvironment within mucosal draining lymph nodes. Nat. Commun. 6, 5862 (2015).

    CAS  PubMed  Google Scholar 

  89. Chu, C. et al. Anti-microbial functions of group 3 innate lymphoid cells in gut-associated lymphoid tissues are regulated by G-protein-coupled receptor 183. Cell Rep. 23, 3750–3758 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Tian, Y. et al. S1PR1-dependent migration of ILC3s from intestinal tissue to the heart in a mouse model of viral myocarditis. J. Leukoc. Biol. 114, 154–163 (2023).

    PubMed  Google Scholar 

  91. Mebius, R. E. Organogenesis of lymphoid tissues. Nat. Rev. Immunol. 3, 292–303 (2003).

    CAS  PubMed  Google Scholar 

  92. Pabst, O. et al. Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling. J. Immunol. 177, 6824–6832 (2006).

    CAS  PubMed  Google Scholar 

  93. Bouskra, D. et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456, 507–510 (2008).

    CAS  PubMed  Google Scholar 

  94. Melo-Gonzalez, F. et al. Antigen-presenting ILC3 regulate T cell-dependent IgA responses to colonic mucosal bacteria. J. Exp. Med. 216, 728–742 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Kruglov, A. A. et al. Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis. Science 342, 1243–1246 (2013).

    CAS  PubMed  Google Scholar 

  96. Okada, S. et al. IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349, 606–613 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Peterson, L. W. & Artis, D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14, 141–153 (2014).

    CAS  PubMed  Google Scholar 

  98. Sonnenberg, G. F., Fouser, L. A. & Artis, D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat. Immunol. 12, 383–390 (2011).

    CAS  PubMed  Google Scholar 

  99. Lindemans, C. A. et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528, 560–564 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. He, G.-W. et al. Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation. Cell Stem Cell 29, 1718–1720 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Romera-Hernández, M. et al. Yap1-driven intestinal repair is controlled by group 3 innate lymphoid cells. Cell Rep. 30, 37–45.e3 (2020).

    PubMed  Google Scholar 

  102. Goto, Y. et al. Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science 345, 1254009 (2014).

    PubMed  PubMed Central  Google Scholar 

  103. Pickard, J. M. et al. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. Nature 514, 638–641 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Pham, T. A. N. et al. Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen. Cell Host Microbe 16, 504–516 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Sugimoto, K. et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J. Clin. Invest. 118, 534–544 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Cash, H. L., Whitham, C. V., Behrendt, C. L. & Hooper, L. V. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313, 1126–1130 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Gaudino, S. J. et al. IL-22 receptor signaling in Paneth cells is critical for their maturation, microbiota colonization, Th17-related immune responses, and anti-Salmonella immunity. Mucosal Immunol. 14, 389–401 (2021).

    CAS  PubMed  Google Scholar 

  108. Keir, M., Yi, T., Lu, T. & Ghilardi, N. The role of IL-22 in intestinal health and disease. J. Exp. Med. 217, e20192195 (2020).

    PubMed  PubMed Central  Google Scholar 

  109. Hepworth, M. R. et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 498, 113–117 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Hepworth, M. R. et al. Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells. Science 348, 1031–1035 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Lyu, M. et al. ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut. Nature 610, 744–751 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Deng, T. et al. ILC3-derived OX40L is essential for homeostasis of intestinal Tregs in immunodeficient mice. Cell. Mol. Immunol. 17, 163–177 (2020).

    CAS  PubMed  Google Scholar 

  113. Wu, X. et al. Group 3 innate lymphoid cells require BATF to regulate gut homeostasis in mice. J. Exp. Med. 219, e20211861 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Abramson, J., Dobeš, J., Lyu, M. & Sonnenberg, G. F. The emerging family of RORγt+ antigen-presenting cells. Nat. Rev. Immunol. 24, 64–77 (2024).

    CAS  PubMed  Google Scholar 

  115. Kim, K. S. et al. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351, 858–863 (2016).

    CAS  PubMed  Google Scholar 

  116. Zhou, L. et al. Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2. Nature 568, 405–409 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Gury-BenAri, M. et al. The spectrum and regulatory landscape of intestinal innate lymphoid cells are shaped by the microbiome. Cell 166, 1231–1246.e13 (2016).

    CAS  PubMed  Google Scholar 

  118. Di Luccia, B., Gilfillan, S., Cella, M., Colonna, M. & Huang, S. C.-C. ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands. J. Exp. Med. 216, 2231–2241 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Krzywinska, E. et al. The transcription factor HIF-1α mediates plasticity of NKp46+ innate lymphoid cells in the gut. J. Exp. Med. 219, e20210909 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Mao, K. et al. Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 554, 255–259 (2018).

    CAS  PubMed  Google Scholar 

  121. Bauché, D. et al. LAG3+ regulatory T cells restrain interleukin-23-producing CX3CR1+ gut-resident macrophages during group 3 innate lymphoid cell-driven colitis. Immunity 49, 342–352.e5 (2018).

    PubMed  Google Scholar 

  122. Wang, X. et al. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes. Nature 514, 237–241 (2014).

    CAS  PubMed  Google Scholar 

  123. Coccia, M. et al. IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cells. J. Exp. Med. 209, 1595–1609 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Korn, L. L. et al. Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells. Mucosal Immunol. 7, 1045–1057 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Sawa, S. et al. RORγt+innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat. Immunol. 12, 320–326 (2011).

    CAS  PubMed  Google Scholar 

  126. Ouahed, J. et al. Very early onset inflammatory bowel disease: a clinical approach with a focus on the role of genetics and underlying immune deficiencies. Inflamm. Bowel Dis. 26, 820–842 (2020).

    PubMed  Google Scholar 

  127. Rankin, L. C. et al. Complementarity and redundancy of IL-22-producing innate lymphoid cells. Nat. Immunol. 17, 179–186 (2016).

    CAS  PubMed  Google Scholar 

  128. Song, C. et al. Unique and redundant functions of NKp46+ ILC3s in models of intestinal inflammation. J. Exp. Med. 212, 1869–1882 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Creyns, B. et al. Fibrogenesis in chronic murine colitis is independent of innate lymphoid cells. Immun. Inflamm. Dis. 8, 393–407 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Bostick, J. W. et al. Dichotomous regulation of group 3 innate lymphoid cells by nongastric Helicobacter species. Proc. Natl Acad. Sci. USA 116, 24760–24769 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Forkel, M. & Mjösberg, J. Dysregulation of group 3 innate lymphoid cells in the pathogenesis of inflammatory bowel disease. Curr. Allergy Asthma Rep. 16, 73 (2016).

    PubMed  PubMed Central  Google Scholar 

  132. Li, J. et al. Enrichment of IL-17A+IFN-γ+ and IL-22+IFN-γ+ T cell subsets is associated with reduction of NKp44+ ILC3s in the terminal ileum of Crohn’s disease patients. Clin. Exp. Immunol. 190, 143–153 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Martin, J. C. et al. Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy. Cell 178, 1493–1508.e20 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Leppkes, M. et al. RORγ-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology 136, 257–267 (2009).

    CAS  PubMed  Google Scholar 

  135. Paustian, A. M. S. et al. Continuous IL-23 stimulation drives ILC3 depletion in the upper GI tract and, in combination with TNFα, induces robust activation and a phenotypic switch of ILC3. PLoS ONE 12, e0182841 (2017).

    PubMed  PubMed Central  Google Scholar 

  136. Zhou, W. et al. ZBTB46 defines and regulates ILC3s that protect the intestine. Nature 609, 159–165 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Villablanca, E. J., Selin, K. & Hedin, C. R. H. Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression? Nat. Rev. Gastroenterol. Hepatol. 19, 493–507 (2022).

    PubMed  Google Scholar 

  138. Hanash, A. M. et al. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity 37, 339–350 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Castro-Dopico, T. et al. GM-CSF calibrates macrophage defense and wound healing programs during intestinal infection and inflammation. Cell Rep. 32, 107857 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Lo, B. C. et al. The transcription factor RORα preserves ILC3 lineage identity and function during chronic intestinal infection. J. Immunol. 203, 3209–3215 (2019).

    CAS  PubMed  Google Scholar 

  141. Zhou, L. et al. Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation. Nat. Immunol. 23, 251–261 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Kaser, A., Zeissig, S. & Blumberg, R. S. Inflammatory bowel disease. Annu. Rev. Immunol. 28, 573–621 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Ananthakrishnan, A. N. Epidemiology and risk factors for IBD. Nat. Rev. Gastroenterol. Hepatol. 12, 205–217 (2015).

    PubMed  Google Scholar 

  144. Maloy, K. J. & Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306 (2011).

    CAS  PubMed  Google Scholar 

  145. Duerr, R. H. et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461–1463 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Barrett, J. C. et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat. Genet. 40, 955–962 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Anderson, C. A. et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat. Genet. 43, 246–252 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat. Genet. 47, 979–986 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Kong, L. et al. The landscape of immune dysregulation in Crohn’s disease revealed through single-cell transcriptomic profiling in the ileum and colon. Immunity 56, 444–458.e5 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Forkel, M. et al. Distinct alterations in the composition of mucosal innate lymphoid cells in newly diagnosed and established Crohn’s disease and ulcerative colitis. J. Crohns Colitis 13, 67–78 (2019).

    PubMed  Google Scholar 

  151. Creyns, B. et al. Biological therapy in inflammatory bowel disease patients partly restores intestinal innate lymphoid cell subtype equilibrium. Front. Immunol. 11, 1847 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Geremia, A. et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J. Exp. Med. 208, 1127–1133 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Takayama, T. et al. Imbalance of NKp44+NKp46– and NKp44–NKp46+ natural killer cells in the intestinal mucosa of patients with Crohn’s disease. Gastroenterology 139, 882–892 (2010).

    CAS  PubMed  Google Scholar 

  154. Xiong, L. et al. Group 3 innate lymphoid cell pyroptosis represents a host defence mechanism against Salmonella infection. Nat. Microbiol. 7, 1087–1099 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. King, J. I. et al. Bcl-2 supports survival and metabolic fitness of quiescent tissue-resident ILC3. Mucosal Immunol. 16, 658–670 (2023).

    PubMed  PubMed Central  Google Scholar 

  156. Friedrich, M., Pohin, M. & Powrie, F. Cytokine networks in the pathophysiology of inflammatory bowel disease. Immunity 50, 992–1006 (2019).

    CAS  PubMed  Google Scholar 

  157. Kobayashi, T. & Hibi, T. Improving IBD outcomes in the era of many treatment options. Nat. Rev. Gastroenterol. Hepatol. 20, 79–80 (2023).

    PubMed  PubMed Central  Google Scholar 

  158. D’Haens, G. R. & van Deventer, S. 25 years of anti-TNF treatment for inflammatory bowel disease: lessons from the past and a look to the future. Gut 70, 1396–1405 (2021).

    PubMed  Google Scholar 

  159. Ninnemann, J. et al. TNF hampers intestinal tissue repair in colitis by restricting IL-22 bioavailability. Mucosal Immunol. 15, 698–716 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Awasthi, A. et al. Cutting edge: IL-23 receptor GFP reporter mice reveal distinct populations of IL-17-producing cells. J. Immunol. 182, 5904–5908 (2009).

    CAS  PubMed  Google Scholar 

  161. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT06052059 (2024).

  162. Lasa, J. S., Olivera, P. A., Danese, S. & Peyrin-Biroulet, L. Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis. Lancet Gastroenterol. Hepatol. 7, 161–170 (2022).

    PubMed  Google Scholar 

  163. Hu, X., Li, J., Fu, M., Zhao, X. & Wang, W. The JAK/STAT signaling pathway: from bench to clinic. Signal. Transduct. Target. Ther. 6, 402 (2021).

    PubMed  PubMed Central  Google Scholar 

  164. Robinette, M. L. et al. Jak3 deficiency blocks innate lymphoid cell development. Mucosal Immunol. 11, 50–60 (2018).

    CAS  PubMed  Google Scholar 

  165. Guo, X. et al. Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection. Immunity 40, 25–39 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Sandborn, W. J. et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N. Engl. J. Med. 369, 711–721 (2013).

    CAS  PubMed  Google Scholar 

  167. Wyant, T., Fedyk, E. & Abhyankar, B. An overview of the mechanism of action of the monoclonal antibody vedolizumab. J. Crohns Colitis 10, 1437–1444 (2016).

    PubMed  Google Scholar 

  168. Kim, E. M. et al. Mucosal eosinophilia is an independent predictor of vedolizumab efficacy in inflammatory bowel diseases. Inflamm. Bowel Dis. 26, 1232–1238 (2020).

    PubMed  Google Scholar 

  169. Zeissig, S. et al. Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease. Gut 68, 25–39 (2019).

    CAS  PubMed  Google Scholar 

  170. Kim, C. H., Hashimoto-Hill, S. & Kim, M. Migration and tissue tropism of innate lymphoid cells. Trends Immunol. 37, 68–79 (2016).

    CAS  PubMed  Google Scholar 

  171. Canales-Herrerias, P. et al. Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis. Preprint at bioRxiv https://doi.org/10.1101/2023.01.19.524731 (2023).

  172. Verstockt, B. et al. Sphingosine 1-phosphate modulation and immune cell trafficking in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 19, 351–366 (2022).

    CAS  PubMed  Google Scholar 

  173. Sandborn, W. J. et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 385, 1280–1291 (2021).

    CAS  PubMed  Google Scholar 

  174. Dutton, E. E. et al. Peripheral lymph nodes contain migratory and resident innate lymphoid cell populations. Sci. Immunol. 4, eaau8082 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Morgan, E. et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut 72, 338–344 (2023).

    PubMed  Google Scholar 

  176. Ikeda, A. et al. Human NKp44+ group 3 innate lymphoid cells associate with tumor-associated tertiary lymphoid structures in colorectal cancer. Cancer Immunol. Res. 8, 724–731 (2020).

    CAS  PubMed  Google Scholar 

  177. Wang, S. et al. Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer. Cell Res. 30, 610–622 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Kirchberger, S. et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J. Exp. Med. 210, 917–931 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Huber, S. et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491, 259–263 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Gronke, K. et al. Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature 566, 249–253 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Tang, L. et al. Immune checkpoint inhibitor-associated colitis: from mechanism to management. Front. Immunol. 12, 800879 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Le, D. T. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357, 409–413 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Kawakami, H., Zaanan, A. & Sinicrope, F. A. Microsatellite instability testing and its role in the management of colorectal cancer. Curr. Treat. Options Oncol. 16, 30 (2015).

    PubMed  PubMed Central  Google Scholar 

  184. Wu, D. et al. PD-1 signaling facilitates activation of lymphoid tissue inducer cells by restraining fatty acid oxidation. Nat. Metab. 4, 867–882 (2022).

    CAS  PubMed  Google Scholar 

  185. Moral, J. A. et al. ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity. Nature 579, 130–135 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Simoni, Y. et al. Human innate lymphoid cell subsets possess tissue-type based heterogeneity in phenotype and frequency. Immunity 46, 148–161 (2017).

    CAS  PubMed  Google Scholar 

  187. Withers, D. R. et al. Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells. Nat. Med. 22, 319–323 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Labanieh, L. & Mackall, C. L. CAR immune cells: design principles, resistance and the next generation. Nature 614, 635–648 (2023).

    CAS  PubMed  Google Scholar 

  189. Baruch, E. N. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371, 602–609 (2021).

    CAS  PubMed  Google Scholar 

  190. Paramsothy, S. et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 389, 1218–1228 (2017).

    PubMed  Google Scholar 

  191. Hrdý, J. et al. Oral supplementation with selected Lactobacillus acidophilus triggers IL-17-dependent innate defense response, activation of innate lymphoid cells type 3 and improves colitis. Sci. Rep. 12, 17591 (2022).

    PubMed  PubMed Central  Google Scholar 

  192. Vély, F. et al. Evidence of innate lymphoid cell redundancy in humans. Nat. Immunol. 17, 1291–1299 (2016).

    PubMed  PubMed Central  Google Scholar 

  193. Basu, R. et al. Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity 37, 1061–1075 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank members of the Sonnenberg Laboratory for discussions and critical reading of the manuscript. Research in the Sonnenberg Laboratory is supported by the National Institutes of Health (R01AI143842, R01AI123368, R01AI145989, U01AI095608, R37AI174468, R01AI162936 and R01CA274534), the NIAID Mucosal Immunology Studies Team (MIST), an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, the Cancer Research Institute, Linda and Glenn Greenberg, the Dalton Family Foundation, and the Roberts Institute for Research in IBD. V.H. is supported by a DFG Walter Benjamin Fellowship (HO 7399/1-1). G.F.S. is a CRI Lloyd J. Old STAR.

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  1. Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA

    Veronika Horn & Gregory F. Sonnenberg

  2. Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology & Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA

    Veronika Horn & Gregory F. Sonnenberg

  3. Department of Microbiology & Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA

    Veronika Horn & Gregory F. Sonnenberg

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Horn, V., Sonnenberg, G.F. Group 3 innate lymphoid cells in intestinal health and disease. Nat Rev Gastroenterol Hepatol 21, 428–443 (2024). https://doi.org/10.1038/s41575-024-00906-3

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