Abraham, C. & Cho, J. H. IL-23 and autoimmunity: new insights into the pathogenesis of inflammatory bowel disease. Annu. Rev. Med. 60, 97–110 (2009).
Maloy, K. J. & Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306 (2011).
Maynard, C. L., Elson, C. O., Hatton, R. D. & Weaver, C. T. Reciprocal interactions of the intestinal microbiota and immune system. Nature 489, 231–241 (2012).
Fragoulis, G. E., Siebert, S. & McInnes, I. B. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu. Rev. Med. 67, 337–353 (2016).
Bernink, J. H. et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat. Immunol. 14, 221–229 (2013).
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).
Zhou, L. et al. Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2. Nature 568, 405–409 (2019).
Oppmann, B. et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13, 715–725 (2000).
Neurath, M. F. IL-23: a master regulator in Crohn disease. Nat. Med. 13, 26–28 (2007).
Krueger, G. G. et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N. Engl. J. Med. 356, 580–592 (2007).
Lubberts, E. The IL-23-IL-17 axis in inflammatory arthritis. Nat. Rev. Rheumatol. 11, 415–429 (2015).
Cua, D. J. et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421, 744–748 (2003).
Duerr, R. H. et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461–1463 (2006).
The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).
D’Haens, G. et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet 399, 2015–2030 (2022).
Feagan, B. G. et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N. Engl. J. Med. 375, 1946–1960 (2016).
Sands, B. E. et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 381, 1201–1214 (2019).
Shih, V. F. et al. Homeostatic IL-23 receptor signaling limits Th17 response through IL-22-mediated containment of commensal microbiota. Proc. Natl Acad. Sci. USA 111, 13942–13947 (2014).
Mangan, P. R. et al. Transforming growth factor-β induces development of the TH17 lineage. Nature 441, 231–234 (2006).
Zheng, Y. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14, 282–289 (2008).
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).
Cox, J. H. et al. Opposing consequences of IL-23 signaling mediated by innate and adaptive cells in chemically induced colitis in mice. Mucosal Immunol. 5, 99–109 (2012).
Izcue, A. et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity 28, 559–570 (2008).
Martínez-Barricarte, R. et al. Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23. Sci. Immunol. 3, eaau6759 (2018).
Mao, K. et al. Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 554, 255–259 (2018).
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).
Sonnenberg, G. F. & Artis, D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat. Med. 21, 698–708 (2015).
Spits, H. et al. Innate lymphoid cells—a proposal for uniform nomenclature. Nat. Rev. Immunol. 13, 145–149 (2013).
Kerdiles, Y. M. et al. Foxo transcription factors control regulatory T cell development and function. Immunity 33, 890–904 (2010).
Hossain, D. M. et al. FoxP3 acts as a cotranscription factor with STAT3 in tumor-induced regulatory T cells. Immunity 39, 1057–1069 (2013).
Jacobse, J. et al. Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells. Cell Rep. 42, 112128 (2023).
Kannan, A. K. et al. IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases. Sci. Rep. 9, 17675 (2019).
Uhlig, H. H. et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25, 309–318 (2006).
Ahern, P. P. et al. Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity 33, 279–288 (2010).
Wing, K. et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 322, 271–275 (2008).
Walker, L. S. & Sansom, D. M. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat. Rev. Immunol. 11, 852–863 (2011).
Chang, T. T., Jabs, C., Sobel, R. A., Kuchroo, V. K. & Sharpe, A. H. Studies in B7-deficient mice reveal a critical role for B7 costimulation in both induction and effector phases of experimental autoimmune encephalomyelitis. J. Exp. Med. 190, 733–740 (1999).
Lenschow, D. J. et al. CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes. Immunity 5, 285–293 (1996).
Tekguc, M., Wing, J. B., Osaki, M., Long, J. & Sakaguchi, S. Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells. Proc. Natl Acad. Sci. USA 118, e2023739118 (2021).
Sugiura, D. et al. Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses. Science 364, 558–566 (2019).
Francisco, L. M. et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J. Exp. Med. 206, 3015–3029 (2009).
Keir, M. E. et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J. Exp. Med. 203, 883–895 (2006).
Lyu, M. et al. ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut. Nature 610, 744–751 (2022).
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).
Jacquelot, N. et al. Immune checkpoints and innate lymphoid cells—new avenues for cancer immunotherapy. Cancers (Basel) 13, 5967 (2021).
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).
Goc, J. et al. Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer. Cell 184, 5015–5030.e5016 (2021).
Kløverpris, H. N. et al. Innate lymphoid cells are depleted irreversibly during acute HIV-1 infection in the absence of viral suppression. Immunity 44, 391–405 (2016).
Page, D. B., Postow, M. A., Callahan, M. K., Allison, J. P. & Wolchok, J. D. Immune modulation in cancer with antibodies. Annu. Rev. Med. 65, 185–202 (2014).
Lo, B. C. et al. Microbiota-dependent activation of CD4+ T cells induces CTLA-4 blockade-associated colitis via Fcγ receptors. Science 383, 62–70 (2024).
Mombaerts, P. et al. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869–877 (1992).
Kühn, R., Löhler, J., Rennick, D., Rajewsky, K. & Müller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263–274 (1993).
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).
Lochner, M. et al. In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells. J. Exp. Med. 205, 1381–1393 (2008).
Narni-Mancinelli, E. et al. Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor. Proc. Natl Acad. Sci. USA 108, 18324–18329 (2011).
Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).
