Monday, May 11, 2026
HomeArthritisInnate lymphoid cells in rheumatoid arthritis as mediators of pathology and resolution

Innate lymphoid cells in rheumatoid arthritis as mediators of pathology and resolution


  • Gravallese, E. M. & Firestein, G. S. Rheumatoid arthritis – common origins, divergent mechanisms. N. Engl. J. Med. 388, 529–542 (2023).

    CAS 
    PubMed 

    Google Scholar 

  • Larid, G., Vix, J., Garlantezec, R., Loppin, E. & Gervais, E. Increased remission with fewer corticosteroids and more biologics in rheumatoid arthritis at 7-year follow-up in real-life conditions. Sci. Rep. 12, 2563 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lillegraven, S. et al. Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial. Ann. Rheum. Dis. 82, 1394–1403 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jarvinen, P. & Aho, K. Twin studies in rheumatic diseases. Semin. Arthritis Rheum. 24, 19–28 (1994).

    CAS 
    PubMed 

    Google Scholar 

  • Bach, J. F. The effect of infections on susceptibility to autoimmune and allergic diseases. N. Engl. J. Med. 347, 911–920 (2002).

    PubMed 

    Google Scholar 

  • Gianfrancesco, M. A. et al. Smoking is associated with higher disease activity in rheumatoid arthritis: a longitudinal study controlling for time-varying covariates. J. Rheumatol. 46, 370–375 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Konig, M. F. et al. Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci. Transl. Med. 8, 369ra176 (2016).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Schmajuk, G., Trupin, L., Yelin, E. & Blanc, P. D. Prevalence of arthritis and rheumatoid arthritis in coal mining counties of the United States. Arthritis Care Res. 71, 1209–1215 (2019).

    CAS 

    Google Scholar 

  • Brusca, S. B., Abramson, S. B. & Scher, J. U. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr. Opin. Rheumatol. 26, 101–107 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arrieta, M. C. et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl. Med. 7, 307ra152 (2015).

    PubMed 

    Google Scholar 

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

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu, H. J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815–827 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

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

    CAS 
    PubMed 

    Google Scholar 

  • Clottu, A. S., Humbel, M., Fluder, N., Karampetsou, M. P. & Comte, D. Innate lymphoid cells in autoimmune diseases. Front. Immunol. 12, 789788 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • Kabil, A. et al. Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell-innate IgE axis. J. Allergy Clin. Immunol. 154, 1260–1276.e9 (2024).

    CAS 
    PubMed 

    Google Scholar 

  • Kabil, A. K. et al. Early-life microbiota skews long-term gene expression and chromatin states of bone marrow hematopoietic precursors. Cell Rep. 45, 116871 (2026).

    CAS 
    PubMed 

    Google Scholar 

  • Kabil, A. K. et al. Microbial dysbiosis sculpts a systemic ILC3/IL-17 axis governing lung inflammatory responses and central hematopoiesis. Mucosal Immunol. 1139–1158, https://doi.org/10.1016/j.mucimm.2025.07.002 (2025).

  • Eberl, G., Colonna, M., Di Santo, J. P. & McKenzie, A. N. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science 348, aaa6566 (2015).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Cherrier, M. & Eberl, G. The development of LTi cells. Curr. Opin. Immunol. 24, 178–183 (2012).

    CAS 
    PubMed 

    Google Scholar 

  • Shin, S. B. & McNagny, K. M. ILC-You in the thymus: a fresh look at innate lymphoid cell development. Front. Immunol. 12, 681110 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jan-Abu, S. C., Kabil, A. & McNagny, K. M. Parallel origins and functions of T cells and ILCs. Clin. Exp. Immunol. 213, 76–86 (2023).

    PubMed 
    PubMed Central 

    Google Scholar 

  • von Moltke, J., Ji, M., Liang, H. E. & Locksley, R. M. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529, 221–225 (2016).

    Google Scholar 

  • Gold, M. J. et al. Group 2 innate lymphoid cells facilitate sensitization to local, but not systemic, TH2-inducing allergen exposures. J. Allergy Clin. Immunol. 133, 1142–1148 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • Halim, T. Y., Krauss, R. H., Sun, A. C. & Takei, F. Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. Immunity 36, 451–463 (2012).

    CAS 
    PubMed 

    Google Scholar 

  • Halim, T. Y. et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity 40, 425–435 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schneider, C. et al. Tissue-Resident Group 2 innate lymphoid cells differentiate by layered ontogeny and in situ perinatal priming. Immunity 50, 1425–1438.e5 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Panda, S. K. & Colonna, M. Innate lymphoid cells in mucosal immunity. Front. Immunol. 10, 861 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, X. et al. Innate lymphoid cells originate from fetal liver-derived tissue-resident progenitors. Sci. Immunol. 10, eadu7962 (2025).

    CAS 
    PubMed 

    Google Scholar 

  • Ghaedi, M. & Takei, F. Innate lymphoid cell development. J. Allergy Clin. Immunol. 147, 1549–1560 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • Simic, M. et al. Distinct waves from the hemogenic endothelium give rise to layered lymphoid tissue inducer cell ontogeny. Cell Rep. 32, 108004 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • Ding, Y. et al. Distinct developmental pathways generate functionally distinct populations of natural killer cells. Nat. Immunol. 25, 1183–1192 (2024).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Harly, C. et al. The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage. Nat. Immunol. 20, 1150–1160 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 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 

  • 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 

  • Zeis, P. et al. In situ maturation and tissue adaptation of type 2 innate lymphoid cell progenitors. Immunity 53, 775–792.e9 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Oherle, K. et al. Insulin-like growth factor 1 supports a pulmonary niche that promotes type 3 innate lymphoid cell development in newborn lungs. Immunity 52, 275–294.e9 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ghaedi, M. et al. Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets. J. Exp. Med. 217, 20182293 (2020).

    Google Scholar 

  • 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 

  • Lo, B. C. et al. The orphan nuclear receptor ROR alpha and group 3 innate lymphoid cells drive fibrosis in a mouse model of Crohn’s disease. Sci. Immunol. 1, eaaf8864 (2016).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Shin, S. B. et al. Abortive γδTCR rearrangements suggest ILC2s are derived from T-cell precursors. Blood Adv. 4, 5362–5372 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Colonna, M. Innate lymphoid cells: diversity, plasticity, and unique functions in immunity. Immunity 48, 1104–1117 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kabil, A., Shin, S. B., Hughes, M. R. & McNagny, K. M. “Just one word, plastic!”: Controversies and caveats in innate lymphoid cell plasticity. Front. Immunol. 13, 946905 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lim, A. I., Verrier, T., Vosshenrich, C. A. & Di Santo, J. P. Developmental options and functional plasticity of innate lymphoid cells. Curr. Opin. Immunol. 44, 61–68 (2017).

    CAS 
    PubMed 

    Google Scholar 

  • Fang, W., Zhang, Y. & Chen, Z. Innate lymphoid cells in inflammatory arthritis. Arthritis Res. Ther. 22, 25 (2020).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu, X. Innate lymphocytes in inflammatory arthritis. Front. Immunol. 11, 565275

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 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 

  • Burrows, K. et al. A gut commensal protozoan determines respiratory disease outcomes by shaping pulmonary immunity. Cell 188, 316–330.e12 (2025).

    CAS 
    PubMed 

    Google Scholar 

  • Sun, X. H. & Bajana, S. ILC differentiation in the thymus. Adv. Exp. Med. Biol. 1365, 25–39 (2022).

    CAS 
    PubMed 

    Google Scholar 

  • Gronke, K., Kofoed-Nielsen, M. & Diefenbach, A. Innate lymphoid cells, precursors and plasticity. Immunol. Lett. 179, 9–18 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • Quatrini, L. et al. Glucocorticoids inhibit human hematopoietic stem cell differentiation toward a common ILC precursor. J. Allergy Clin. Immunol. 149, 1772–1785 (2022).

    CAS 
    PubMed 

    Google Scholar 

  • 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 

  • Cherrier, D. E., Serafini, N. & Di Santo, J. P. Innate lymphoid cell development: a T cell perspective. Immunity 48, 1091–1103 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • Yu, H., Jacquelot, N. & Belz, G. T. Metabolic features of innate lymphoid cells. J. Exp. Med. 219, e20221140 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Surace, L. et al. Dichotomous metabolic networks govern human ILC2 proliferation and function. Nat. Immunol. 22, 1367–1374 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhou, L., Lin, Q. & Sonnenberg, G. F. Metabolic control of innate lymphoid cells in health and disease. Nat. Metab. 4, 1650–1659 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hodge, S. H. et al. Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses. J. Exp. Med. 220, e20221073 (2023).

    CAS 
    PubMed 

    Google Scholar 

  • Fu, L. et al. A mitochondrial STAT3-methionine metabolism axis promotes ILC2-driven allergic lung inflammation. J. Allergy Clin. Immunol. 149, 2091–2104 (2022).

    CAS 
    PubMed 

    Google Scholar 

  • Ham, J., Yang, W. & Kim, H. Y. Tissue-specific metabolic reprogramming in innate lymphoid cells and its impact on disease. Immune Netw. 25, e3 (2025).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Kania, A. K., Kokkinou, E., Pearce, E. & Pearce, E. Metabolic adaptations of ILC2 and Th2 cells in type 2 immunity. Curr. Opin. Immunol. 91, 102503 (2024).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zheng, Q. H., Zhai, Y., Wang, Y. H. & Pan, Z. The role of hypoxic microenvironment in rheumatoid arthritis. Front. Immunol. 16, 1633406 (2025).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chimenti, M. S. et al. The interplay between inflammation and metabolism in rheumatoid arthritis. Cell Death Dis. 6, e1887 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Molofsky, A. B. & Locksley, R. M. The ins and outs of innate and adaptive type 2 immunity. Immunity 56, 704–722 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Eberl, G. Immunity by equilibrium. Nat. Rev. Immunol. 16, 524–532 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • Gieseck, R. L. 3rd, Wilson, M. S. & Wynn, T. A. Type 2 immunity in tissue repair and fibrosis. Nat. Rev. Immunol. 18, 62–76 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • Rauber, S. et al. Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells. Nat. Med. 23, 938–944 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hirota, K. et al. Autoimmune Th17 cells induced synovial stromal and innate lymphoid cell Secretion of the cytokine GM-CSF to initiate and augment autoimmune arthritis. Immunity 48, 1220–1232.e5 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Omata, Y. et al. Group 2 innate lymphoid cells attenuate inflammatory arthritis and protect from bone destruction in mice. Cell Rep. 24, 169–180 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • Kabil, A. et al. Functional targeting of ILC2s and ILC3s reveals selective roles in intestinal fibrosis and homeostasis. J. Exp. Med. 222, e20241671 (2025).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bando, J. K. et al. ILC2s are the predominant source of intestinal ILC-derived IL-10. J. Exp. Med. 217, e20191520 (2020).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, D. et al. IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner. Sci. Rep. 6, 36002 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fallon, P. G. et al. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J. Exp. Med. 203, 1105–1116 (2006).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sakaguchi, N. et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426, 454–460 (2003).

    CAS 
    PubMed 

    Google Scholar 

  • Keller, K. K. et al. SKG arthritis as a model for evaluating therapies in rheumatoid arthritis with special focus on bone changes. Rheumatol. Int. 33, 1127–1133 (2013).

    CAS 
    PubMed 

    Google Scholar 

  • Hirota, K. et al. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J. Exp. Med. 204, 41–47 (2007).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cook, A. D., Braine, E. L., Campbell, I. K., Rich, M. J. & Hamilton, J. A. Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res. 3, 293–298 (2001).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cook, A. D. et al. TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17. JCI Insight 3, e99249 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee, K. M. C., Achuthan, A. A. & Hamilton, J. A. GM-CSF: a promising target in inflammation and autoimmunity. Immunotargets Ther. 9, 225–240 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hamilton, J. A., Cook, A. D. & Tak, P. P. Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases. Nat. Rev. Drug. Discov. 16, 53–70 (2016).

    PubMed 

    Google Scholar 

  • Nakae, S., Nambu, A., Sudo, K. & Iwakura, Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J. Immunol. 171, 6173–6177 (2003).

    CAS 
    PubMed 

    Google Scholar 

  • 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 

  • Cua, D. J. & Tato, C. M. Innate IL-17-producing cells: the sentinels of the immune system. Nat. Rev. Immunol. 10, 479–489 (2010).

    CAS 
    PubMed 

    Google Scholar 

  • 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).

    CAS 
    PubMed 

    Google Scholar 

  • Murphy, C. A. et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med. 198, 1951–1957 (2003).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cornelissen, F. et al. Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORγt in γδ T cells. Arthritis Res. Ther. 11, R194 (2009).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Takaki-Kuwahara, A. et al. CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines. Arthritis Res. Ther. 21, 198 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, T. et al. Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis. Clin. Rheumatol. 41, 3837–3849 (2022).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Melo-Gonzalez, F. & Hepworth, M. R. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells. Immunology 150, 265–275 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rodriguez-Carrio, J. et al. Brief report: altered innate lymphoid cell subsets in human lymph node biopsy specimens obtained during the at-risk and earliest phases of rheumatoid arthritis. Arthritis Rheumatol. 69, 70–76 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chan, T. Y. et al. Increased ILC3s associated with higher levels of IL-1β aggravates inflammatory arthritis in mice lacking phagocytic NADPH oxidase. Eur. J. Immunol. 49, 2063–2073 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Leijten, E. F. et al. Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheumatol. 67, 2673–2678 (2015).

    PubMed 

    Google Scholar 

  • Liu, X. et al. Group 3 innate lymphoid cells promotes Th17 cells differentiation in rheumatoid arthritis. Clin. Exp. Rheumatol. 42, 2183–2193 (2024).

    CAS 
    PubMed 

    Google Scholar 

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

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rodrigues, P. F. et al. Rorδt-positive dendritic cells are required for the induction of peripheral regulatory T cells in response to oral antigens. Cell 188, 2720–2737.e22 (2025).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ulezko Antonova, A. et al. A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells. Proc. Natl Acad. Sci. USA 120, e2318710120 (2023).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Akagbosu, B. et al. Novel antigen-presenting cell imparts Treg-dependent tolerance to gut microbiota. Nature 610, 752–760 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kedmi, R. et al. A RORγt+ cell instructs gut microbiota-specific Treg cell differentiation. Nature 610, 737–743 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cabric, V. et al. A wave of Thetis cells imparts tolerance to food antigens early in life. Science 389, 268–274 (2025).

    CAS 
    PubMed 

    Google Scholar 

  • Croft, A. P. et al. Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage. Arthritis Res. Ther. 18, 270 (2016).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Orange, D. E. et al. RNA identification of PRIME cells predicting rheumatoid arthritis flares. N. Engl. J. Med. 383, 218–228 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dahlgren, M. W. et al. Adventitial stromal cells define group 2 innate lymphoid cell tissue niches. Immunity 50, 707–722.e6 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Qian, H. et al. Targeting pathogenic fibroblast-like synoviocyte subsets in rheumatoid arthritis. Arthritis Res. Ther. 26, 103 (2024).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Rauber, S. et al. CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis. Nat. Immunol. 25, 682–692 (2024).

    CAS 
    PubMed 

    Google Scholar 

  • Sun, J. C., Beilke, J. N. & Lanier, L. L. Adaptive immune features of natural killer cells. Nature 457, 557–561 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Weizman, O. E. et al. Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12. Nat. Immunol. 20, 1004–1011 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Klose, C. S. N. & Artis, D. Innate lymphoid cells control signaling circuits to regulate tissue-specific immunity. Cell Res. 30, 475–491 (2020).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Biniaris-Georgallis, S. I. et al. Amplification of autoimmune organ damage by NKp46-activated ILC1s. Nature 634, 952–960 (2024).

    CAS 
    PubMed 

    Google Scholar 

  • Yang, F. et al. Dysregulation of innate lymphoid cells in patients with active rheumatoid arthritis and mice with collagen-induced arthritis. Mediators Inflamm. 2021, 1915068 (2021).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Sparano, C. et al. Embryonic and neonatal waves generate distinct populations of hepatic ILC1s. Sci. Immunol. 7, eabo6641 (2022).

    CAS 
    PubMed 

    Google Scholar 

  • Cutolo, M., Campitiello, R., Gotelli, E. & Soldano, S. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front. Immunol. 13, 867260 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mackay, L. K. et al. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 352, 459–463 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • Yomogida, K. et al. Hobit confers tissue-dependent programs to type 1 innate lymphoid cells. Proc. Natl Acad. Sci. USA 118, e2117965118 (2021).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Ducimetiere, L. et al. Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis. Proc. Natl Acad. Sci. USA 118, e2026271118 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Woods, J. M., Haines, G. K., Shah, M. R., Rayan, G. & Koch, A. E. Low-level production of interleukin-13 in synovial fluid and tissue from patients with arthritis. Clin. Immunol. Immunopathol. 85, 210–220 (1997).

    CAS 
    PubMed 

    Google Scholar 

  • Iwaszko, M., Bialy, S. & Bogunia-Kubik, K. Significance of interleukin (IL)-4 and IL-13 in inflammatory arthritis. Cells 10, 3000 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ciccia, F. et al. Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann. Rheum. Dis. 74, 1739–1747 (2015).

    CAS 
    PubMed 

    Google Scholar 

  • Ciccia, F. et al. Proinflammatory CX3CR1+CD59+tumor necrosis factor-like molecule 1A+interleukin-23+ monocytes are expanded in patients with ankylosing spondylitis and modulate innate lymphoid cell 3 immune functions. Arthritis Rheumatol. 70, 2003–2013 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • Inamo, J. et al. Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis. J. Clin. Invest. 135, e185217 (2025).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lundberg, M. et al. Multiplexed homogeneous proximity ligation assays for high-throughput protein biomarker research in serological material. Mol. Cell Proteom. 10, M110 004978 (2011).

    Google Scholar 

  • Van Acker, N. et al. Spatial mapping of innate lymphoid cells in human lymphoid tissues and lymphoma at single-cell resolution. Nat. Commun. 16, 4545 (2025).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 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 

  • Hashemi, E., McCarthy, C., Rao, S. & Malarkannan, S. Transcriptomic diversity of innate lymphoid cells in human lymph nodes compared to BM and spleen. Commun. Biol. 7, 769 (2024).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Qi, J. et al. Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression. Cell Rep. Med. 2, 100353 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Krausgruber, T. et al. Single-cell and spatial transcriptomics reveal aberrant lymphoid developmental programs driving granuloma formation. Immunity 56, 289–306.e287 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Young, J., Inamo, J., Caterer, Z., Krishna, R. & Zhang, F. CellPhenoX: an explainable machine learning method for identifying cell phenotypes to predict clinical outcomes from single-cell multi-omics. Adv. Sci. 12, e03289 https://doi.org/10.1002/advs.202503289e03289 (2025).

  • Kuo, I. C., Brassard, J., Zandstra, P. W. & McNagny, K. M. Innate lymphoid cells in the spotlight: from biomarkers to blueprint for innovative immunotherapy. Front. Immunol. 16, 1655730 (2025).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Howard, E. et al. IL-10 production by ILC2s requires Blimp-1 and cMaf, modulates cellular metabolism, and ameliorates airway hyperreactivity. J. Allergy Clin. Immunol. 147, 1281–1295.e5 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • Seehus, C. R. et al. Alternative activation generates IL-10 producing type 2 innate lymphoid cells. Nat. Commun. 8, 1900 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, S. et al. Selective targeting of PI3Kδ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases. J. Autoimmun. 111, 102435 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • Lo Pizzo, M. et al. JAK/STAT inhibition modifies the ILC1 immune response in patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 42, 593–600 (2024).

    PubMed 

    Google Scholar 

  • Stabile, H. et al. JAK/STAT signaling in regulation of innate lymphoid cells: the gods before the guardians. Immunol. Rev. 286, 148–159 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kato, M. et al. Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokines/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis. PLoS ONE 16, e0252116 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arra, A. et al. PD1+ innate lymphoid cells 3 predict JAK-dependent inflammation in rheumatoid arthritis. J. Autoimmun. 154, 103424 (2025).

    CAS 
    PubMed 

    Google Scholar 

  • Colpitts, S. J. et al. Cell therapy with human interleukin 10-producing ILC2s enhances islet function and inhibits allograft rejection. Am. J. Transpl. 25, 1858–1869 (2025).

    CAS 

    Google Scholar 

  • Reid, K. T. et al. Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses. Cell Rep. 44, 115102 (2025).

    CAS 
    PubMed 

    Google Scholar 

  • Wright, G. P. et al. Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis. Proc. Natl Acad. Sci. USA 106, 19078–19083 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Asnagli, H. et al. Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis. Arthritis Res. Ther. 16, R115 (2014).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, T. et al. Regulatory T cells in rheumatoid arthritis showed increased plasticity toward Th17 but retained suppressive function in peripheral blood. Ann. Rheum. Dis. 74, 1293–1301 (2015).

    CAS 
    PubMed 

    Google Scholar 

  • Van Steendam, K. et al. Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins. Arthritis Res. Ther. 12, R132 (2010).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, S. et al. Strength of CAR signaling determines T cell versus ILC differentiation from pluripotent stem cells. Cell Rep. 42, 112241 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Halim, T. Y. F. Emerging in vivo tools for ILC2 research. J. Exp. Med. 222, e20250883 (2025).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • RELATED ARTICLES

    LEAVE A REPLY

    Please enter your comment!
    Please enter your name here

    Most Popular

    Recent Comments