{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:13:25Z","timestamp":1788790405257,"version":"build-2803163510"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inflammatory bowel disease (IBD), which includes Crohn\u2019s disease (CD) and ulcerative colitis (UC), is a group of chronic gastrointestinal inflammatory diseases characterized by persistent mucosal inflammation and intestinal immune barrier dysfunction. Innate lymphoid cells (ILCs) are key regulators of mucosal immunity; however, the contribution of their context-dependent plasticity to IBD-associated immune barrier remodeling remains incompletely defined. This narrative review summarizes the intestinal distribution and functional specialization of ILC subsets, their dysregulation in the IBD microenvironment, and the molecular signals that regulate ILC plasticity. Current evidence most strongly supports an ILC3-to-ILC1 transition in CD, whereas direct evidence for defined directional ILC plasticity in UC and for ILC2 lineage conversion in intestinal IBD remains limited. We also discuss the context-dependent roles of ILC2s in epithelial repair, inflammation, and fibrosis, as well as the functional reprogramming of ILC3s from barrier-protective to potentially pathogenic states. In addition, this review summarizes the cytokine, transcriptional, epigenetic, and metabolic mechanisms associated with ILC fate remodeling and discusses potential therapeutic strategies targeting these pathways. Overall, ILC plasticity may represent a disease- and tissue-specific mechanism contributing to intestinal immune barrier remodeling, although its causal role and therapeutic relevance require further validation in human IBD. These findings provide a framework for developing more precisely stratified and context-dependent therapeutic approaches for IBD.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1891742","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:18:02Z","timestamp":1788787082000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ILC plasticity in intestinal immune barrier remodeling: current evidence and therapeutic implications for inflammatory bowel disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Ziqing","family":"Zhou","sequence":"first","affiliation":[{"name":"The Second Clinical Medical College, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ling","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shen","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1159\/000527452","article-title":"Significance of 5-aminosalicylic acid intolerance in the clinical management of ulcerative colitis","volume":"104","author":"Mikami","year":"2023","journal-title":"Digestion"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-97-7640-5_30","article-title":"Inflammatory bowel disease","volume":"361","author":"Abraham","year":"2009","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.21203\/rs.3.rs-4810674\/v1","article-title":"Global, regional, and national burden of inflammatory bowel disease, 1990-2021: Insights from the global burden of disease 2021","volume":"39","author":"Lin","year":"2024","journal-title":"Int J Colorectal Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.70109","article-title":"Intestinal ILC-epithelial cell circuits shaping barrier immunity","volume":"104","author":"Yu","year":"2026","journal-title":"Immunol Cell Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05711.x","article-title":"Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation","author":"Koboziev","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1237-9","article-title":"Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases","volume":"569","author":"Lloyd-Price","year":"2019","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.029","article-title":"Intra- and inter-cellular rewiring of the human colon during ulcerative colitis","volume":"178","author":"Smillie","year":"2019","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2024.06.006","article-title":"JAK\/STAT signaling promotes the emergence of unique cell states in ulcerative colitis","volume":"19","author":"Maciag","year":"2024","journal-title":"Stem Cell Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.13376\/j.cbls\/2017117","article-title":"The pathogenesis and immunotherapies of inflammatory bowel disease","volume":"29","author":"Guo","year":"2017","journal-title":"Chinese J Life Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1461297","article-title":"Immunotherapy in inflammatory bowel disease: Novel and emerging treatments","volume":"14","author":"Catalan-Serra","year":"2018","journal-title":"Hum Vaccin Immunother"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.07.014","article-title":"Stricturing Crohn's disease single-cell RNA sequencing reveals fibroblast heterogeneity and intercellular interactions","volume":"165","author":"Mukherjee","year":"2023","journal-title":"Gastroenterology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116502","article-title":"Goblet cell-expressed microprotein FXYD3 determines gut homeostasis by maintaining mucus barrier integrity","volume":"44","author":"Yang","year":"2025","journal-title":"Cell Rep"},{"key":"B13","article-title":"Roles of innate lymphoid cells in tumor immunity and their clinical significance","volume":"39","author":"Chai","year":"2019","journal-title":"Chin J Microbiol Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.019","article-title":"Interleukin-12 and -23 control plasticity of CD127(+) group 1 and group 3 innate lymphoid cells in the intestinal lamina propria","volume":"43","author":"Bernink","year":"2015","journal-title":"Immunity"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502673","article-title":"Phenotypic and functional plasticity of murine intestinal NKp46+ group 3 innate lymphoid cells","volume":"196","author":"Verrier","year":"2016","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nri3365","article-title":"Innate lymphoid cells--a proposal for uniform nomenclature","volume":"13","author":"Spits","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.030","article-title":"Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages","volume":"157","author":"Klose","year":"2014","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.017","article-title":"Innate lymphoid cells: 10 years on","volume":"174","author":"Vivier","year":"2018","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4854","DOI":"10.1038\/s41467-018-07405-5","article-title":"Memory formation and long-term maintenance of IL-7R\u03b1(+) ILC1s via a lymph node-liver axis","volume":"9","author":"Wang","year":"2018","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2534","article-title":"Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues","volume":"14","author":"Bernink","year":"2013","journal-title":"Nat Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.010","article-title":"Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-\u03b3-producing cells","volume":"38","author":"Fuchs","year":"2013","journal-title":"Immunity"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.903688","article-title":"Helper-like type-1 innate lymphoid cells in inflammatory bowel disease","volume":"13","author":"Coman","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.022","article-title":"Tissue determinants of human NK cell development, function, and residence","volume":"180","author":"Dogra","year":"2020","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/nri3839","article-title":"Perforin and granzymes: function, dysfunction and human pathology","volume":"15","author":"Voskoboinik","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.bj.2020.10.001","article-title":"Type 1 innate lymphoid cells: Soldiers at the front line of immunity","volume":"44","author":"Nabekura","year":"2020","journal-title":"Biomed J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/ecco-jcc\/jjy119","article-title":"Distinct alterations in the composition of mucosal innate lymphoid cells in newly diagnosed and established Crohn\u2019s disease and ulcerative colitis","volume":"13","author":"Forkel","year":"2019","journal-title":"J Crohn's Colitis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s13062-023-00401-w","article-title":"ILC1-derived IFN-\u03b3 regulates macrophage activation in colon cancer","volume":"18","author":"Zhang","year":"2023","journal-title":"Biol Direct"},{"key":"B28","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.cell.2017.09.052","article-title":"ILC1 confer early host protection at initial sites of viral infection","volume":"171","author":"Weizman","year":"2017","journal-title":"Cell"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nature11813","article-title":"A T-bet gradient controls the fate and function of CCR6-ROR\u03b3t+ innate lymphoid cells","volume":"494","author":"Klose","year":"2013","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2019.1667723","article-title":"Enteric bacteria induce IFN\u03b3 and Granzyme B from human colonic group 1 innate lymphoid cells","volume":"12","author":"Castleman","year":"2020","journal-title":"Gut Microbes"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3094","article-title":"Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets","volume":"16","author":"Robinette","year":"2015","journal-title":"Nat Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41392-021-00705-1","article-title":"Local tissue development of type 1 innate lymphoid cells: guided by interferon-gamma","volume":"6","author":"Conlon","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03214.x","article-title":"Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice","volume":"146","author":"Ito","year":"2006","journal-title":"Clin Exp Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.04.012","article-title":"Neutralization of IL-6 and TNF-\u03b1 ameliorates intestinal permeability in DSS-induced colitis","volume":"83","author":"Xiao","year":"2016","journal-title":"Cytokine"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.609400","article-title":"CCR8 signaling via CCL1 regulates responses of intestinal IFN-\u03b3 producing innate lymphoid cells and protects from experimental colitis","volume":"11","author":"Kang","year":"2020","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5610","DOI":"10.1038\/s41467-024-49881-y","article-title":"Stage-specific GATA3 induction promotes ILC2 development after lineage commitment","volume":"15","author":"Furuya","year":"2024","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/s41420-024-02096-y","article-title":"Tissue microenvironment induces tissue specificity of ILC2","volume":"10","author":"Qin","year":"2024","journal-title":"Cell Death Discov"},{"key":"B38","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.1038\/s41467-025-59811-1","article-title":"Spatial mapping of innate lymphoid cells in human lymphoid tissues and lymphoma at single-cell resolution","volume":"16","author":"Van Acker","year":"2025","journal-title":"Nat Commun"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.202.supp.129.1","article-title":"Adventitial stromal cells define group 2 innate lymphoid cell tissue niches","volume":"50","author":"Dahlgren","year":"2019","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.cell.2014.12.011","article-title":"Activated type 2 innate lymphoid cells regulate beige fat biogenesis","volume":"160","author":"Lee","year":"2015","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142224","article-title":"Bcl11b is essential for group 2 innate lymphoid cell development","volume":"212","author":"Walker","year":"2015","journal-title":"J Exp Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.01.012","article-title":"The transcription factor GATA3 is critical for the development of all IL-7R\u03b1-expressing innate lymphoid cells","volume":"40","author":"Yagi","year":"2014","journal-title":"Immunity"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3078","article-title":"IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells","volume":"16","author":"Huang","year":"2015","journal-title":"Nat Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nature16161","article-title":"Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit","volume":"529","author":"von Moltke","year":"2016","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(01)00243-6","article-title":"IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo","volume":"15","author":"Fort","year":"2001","journal-title":"Immunity"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1038\/s41467-017-02023-z","article-title":"Alternative activation generates IL-10 producing type 2 innate lymphoid cells","volume":"8","author":"Seehus","year":"2017","journal-title":"Nat Commun"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130351","article-title":"A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis","volume":"210","author":"Salimi","year":"2013","journal-title":"J Exp Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/nature12526","article-title":"Type 2 innate lymphoid cells control eosinophil homeostasis","volume":"502","author":"Nussbaum","year":"2013","journal-title":"Nature"},{"key":"B49","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nm1332","article-title":"IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis","volume":"12","author":"Fichtner-","year":"2006","journal-title":"Nat Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.016","article-title":"MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion","volume":"41","author":"Oliphant","year":"2014","journal-title":"Immunity"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.576929","article-title":"Neural regulation of interactions between group 2 innate lymphoid cells and pulmonary immune cells","volume":"11","author":"Chen","year":"2020","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509070112","article-title":"IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions","volume":"112","author":"Monticelli","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"B53","doi-asserted-by":"publisher","first-page":"7618","DOI":"10.3390\/ijms22147618","article-title":"Innate lymphoid cells in intestinal homeostasis and inflammatory bowel disease","volume":"22","author":"Saez","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B54","doi-asserted-by":"publisher","first-page":"598","DOI":"10.4049\/jimmunol.1800292","article-title":"IL-33 induces murine intestinal goblet cell differentiation indirectly via innate lymphoid cell IL-13 secretion","volume":"202","author":"Waddell","year":"2019","journal-title":"J Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5018975","article-title":"ILC2 proliferated by IL-33 stimulation alleviates acute colitis in Rag1(-\/-) mouse through promoting M2 macrophage polarization","volume":"2020","author":"You","year":"2020","journal-title":"J Immunol Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867351","article-title":"Heterogeneity of ILC2s in the intestine; homeostasis and pathology","volume":"13","author":"Sunaga","year":"2022","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1093\/intimm\/dxv052","article-title":"Differentiation and function of group 3 innate lymphoid cells, from embryo to adult","volume":"28","author":"van de Pavert","year":"2016","journal-title":"Int Immunol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.coi.2015.11.005","article-title":"Differentiation of human innate lymphoid cells (ILCs)","volume":"38","author":"Juelke","year":"2016","journal-title":"Curr Opin Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747388","article-title":"Mouse models for the study of fate and function of innate lymphoid cells","volume":"48","author":"Cording","year":"2018","journal-title":"Eur J Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/nature08949","article-title":"Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology","volume":"464","author":"Buonocore","year":"2010","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.immuni.2013.10.021","article-title":"Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection","volume":"40","author":"Guo","year":"2014","journal-title":"Immunity"},{"key":"B62","article-title":"Research advances on the role of type 3 innate lymphoid cells in the evolution of the immune system","volume":"39","author":"Xian","year":"2023","journal-title":"Chinese Journal of Cellular and Molecular Immunology"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.008","article-title":"The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells","volume":"37","author":"Powell","year":"2012","journal-title":"Immunity"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12996","article-title":"Enrichment of IL-17A(+) IFN-gamma(+) and IL-22(+) IFN-gamma(+) T cell subsets is associated with reduction of NKp44(+) ILC3s in the terminal ileum of Crohn's disease patients","volume":"190","author":"Li","year":"2017","journal-title":"Clin Exp Immunol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"5841","DOI":"10.1038\/s41467-021-26187-x","article-title":"CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn's disease","volume":"12","author":"Krabbendam","year":"2021","journal-title":"Nat Commun"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.06.23295056","article-title":"Single-cell RNA sequencing of terminal ileal biopsies identifies signatures of Crohn's disease pathogenesis","volume":"58","author":"Krzak","year":"2026","journal-title":"Nat Genet"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.10.017","article-title":"The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon","volume":"56","author":"Kong","year":"2023","journal-title":"Immunity"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1254\/jpssuppl.wcp2018.0_sy78-2","article-title":"Subsets of ILC3-ILC1-like cells generate a diversity spectrum of innate lymphoid cells in human mucosal tissues","volume":"20","author":"Cella","year":"2019","journal-title":"Nat Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151750","article-title":"IL-12 drives functional plasticity of human group 2 innate lymphoid cells","volume":"213","author":"Lim","year":"2016","journal-title":"J Exp Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02261-0","article-title":"Epigenetic imprinting in innate lymphoid cell precursors directs the lineage segregation of innate lymphoid cells","volume":"26","author":"Liu","year":"2025","journal-title":"Nat Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01137-5","article-title":"Epigenetic programming defines haematopoietic stem cell fate restriction","volume":"25","author":"Meng","year":"2023","journal-title":"Nat Cell Biol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1042\/bst20200737","article-title":"Heterochromatin and Polycomb as regulators of haematopoiesis","volume":"49","author":"Keenan","year":"2021","journal-title":"Biochem Soc Trans"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.07.008","article-title":"Inflammation and the intestinal barrier: Leukocyte-epithelial cell interactions, cell junction remodeling, and mucosal repair","volume":"151","author":"Luissint","year":"2016","journal-title":"Gastroenterology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1002\/path.70019","article-title":"Crohn's lymphoid aggregates with endothelial clusters colocalise with submucosal fibrosis in fibrostenosing Crohn's disease","volume":"268","author":"Glinka","year":"2026","journal-title":"J Pathol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317571","article-title":"Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis","volume":"68","author":"van der Post","year":"2019","journal-title":"Gut"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1042\/bst20210535","article-title":"Type 2 immunity in intestinal homeostasis and inflammatory bowel disease","volume":"49","author":"Luo","year":"2021","journal-title":"Biochem Soc Trans"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.10","article-title":"Group 3 innate lymphoid cells regulate neutrophil migration and function in human decidua","volume":"9","author":"Croxatto","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"8280","DOI":"10.1038\/ncomms9280","article-title":"NCR(+)ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures","volume":"6","author":"Carrega","year":"2015","journal-title":"Nat Commun"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.196.supp.67.2","article-title":"Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4(+) T cells","volume":"348","author":"Hepworth","year":"2015","journal-title":"Science"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01024-x","article-title":"Reciprocal transcription factor networks govern tissue-resident ILC3 subset function and identity","volume":"22","author":"Fiancette","year":"2021","journal-title":"Nat Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.13294\/j.aps.2022.0012","article-title":"Roles of group 3 innate lymphoid cells in inflammatory diseases","volume":"74","author":"Xie","year":"2022","journal-title":"Acta Physiol Sin"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.14800\/ics.1404","article-title":"Aryl hydrocarbon receptor signaling involves in the human intestinal ILC3\/ILC1 conversion in the inflamed terminal ileum of Crohn's disease patients","volume":"3","author":"Li","year":"2016","journal-title":"Inflammation Cell Signal"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155425","article-title":"Wogonin improves colitis by activating the AhR pathway to regulate the plasticity of ILC3\/ILC1","volume":"128","author":"Ye","year":"2024","journal-title":"Phytomedicine"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3447","article-title":"IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity","volume":"17","author":"Ohne","year":"2016","journal-title":"Nat Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3444","article-title":"IL-1\u03b2, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs","volume":"17","author":"Bal","year":"2016","journal-title":"Nat Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3443","article-title":"Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs","volume":"17","author":"Silver","year":"2016","journal-title":"Nat Immunol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1038\/s41590-019-0423-0","article-title":"c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies","volume":"20","author":"Bernink","year":"2019","journal-title":"Nat Immunol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202350379","article-title":"Epigenetic regulation of innate lymphoid cells","volume":"54","author":"Sun","year":"2024","journal-title":"Eur J Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.043","article-title":"The spectrum and regulatory landscape of intestinal innate lymphoid cells are shaped by the microbiome","volume":"166","author":"Gury-BenAri","year":"2016","journal-title":"Cell"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00453-7","article-title":"Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging","volume":"3","author":"Shen","year":"2023","journal-title":"Nat Aging"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.029","article-title":"Developmental acquisition of regulomes underlies innate lymphoid cell functionality","volume":"165","author":"Shih","year":"2016","journal-title":"Cell"},{"key":"B92","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41385-020-0317-3","article-title":"Brg1 restrains the pro-inflammatory properties of ILC3s and modulates intestinal immunity","volume":"14","author":"Qi","year":"2021","journal-title":"Mucosal Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151646","article-title":"G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program","volume":"213","author":"Antignano","year":"2016","journal-title":"J Exp Med"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191030","article-title":"c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program","volume":"217","author":"Parker","year":"2020","journal-title":"J Exp Med"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116862","article-title":"H3K27-specific demethylase orchestrates the phenotypic and functional plasticity of intestinal ILC3s","volume":"45","author":"Gao","year":"2026","journal-title":"Cell Rep"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180549","article-title":"ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands","volume":"216","author":"Di Luccia","year":"2019","journal-title":"J Exp Med"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-020-00371-6","article-title":"Hypoxia enhances ILC3 responses through HIF-1alpha-dependent mechanism","volume":"14","author":"Fachi","year":"2021","journal-title":"Mucosal Immunol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115456","article-title":"The metabolic sensor LKB1 regulates ILC3 homeostasis and mitochondrial function","volume":"44","author":"Fonseca-Pereira","year":"2025","journal-title":"Cell Rep"},{"key":"B99","doi-asserted-by":"publisher","first-page":"4462","DOI":"10.1038\/s41467-021-24755-9","article-title":"Mitochondrial transcription factor A in RORgammat(+) lymphocytes regulate small intestine homeostasis and metabolism","volume":"12","author":"Fu","year":"2021","journal-title":"Nat Commun"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01043-8","article-title":"Dichotomous metabolic networks govern human ILC2 proliferation and function","volume":"22","author":"Surace","year":"2021","journal-title":"Nat Immunol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151448","article-title":"Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection","volume":"213","author":"Wilhelm","year":"2016","journal-title":"J Exp Med"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.017","article-title":"Regulated expression of nuclear receptor ROR\u03b3t confers distinct functional fates to NK cell receptor-expressing ROR\u03b3t(+) innate lymphocytes","volume":"33","author":"Vonarbourg","year":"2010","journal-title":"Immunity"},{"key":"B103","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1038\/s41467-019-09883-7","article-title":"IL-1\u03b2, IL-23, and TGF-\u03b2 drive plasticity of human ILC2s towards IL-17-producing ILCs in nasal inflammation","volume":"10","author":"Golebski","year":"2019","journal-title":"Nat Commun"},{"key":"B104","doi-asserted-by":"publisher","first-page":"9770","DOI":"10.1038\/s41467-024-54174-5","article-title":"Mechanics-activated fibroblasts promote pulmonary group 2 innate lymphoid cell plasticity propelling silicosis progression","volume":"15","author":"He","year":"2024","journal-title":"Nat Commun"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3800","article-title":"Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells","volume":"18","author":"Gao","year":"2017","journal-title":"Nat Immunol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-18-3458","article-title":"IL23-Producing human lung cancer cells promote tumor growth via conversion of innate lymphoid cell 1 (ILC1) into ILC3","volume":"25","author":"Koh","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B107","doi-asserted-by":"publisher","first-page":"5015","DOI":"10.1016\/j.cell.2021.07.029","article-title":"Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer","volume":"184","author":"Goc","year":"2021","journal-title":"Cell"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1947","article-title":"IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46","volume":"11","author":"Eisenring","year":"2010","journal-title":"Nat Immunol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-325288","article-title":"The tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma","volume":"71","author":"Heinrich","year":"2022","journal-title":"Gut"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02180","article-title":"The obese liver environment mediates conversion of NK cells to a less cytotoxic ILC1-like phenotype","volume":"10","author":"Cuff","year":"2019","journal-title":"Front Immunol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.02.025","article-title":"Five-year efficacy and safety of ustekinumab treatment in Crohn's disease: The IM-UNITI trial","volume":"20","author":"Sandborn","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B112","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3390\/pharmacy13030073","article-title":"Ustekinumab in the treatment of Crohn's disease-a narrative review on clinical efficacy and safety profile","volume":"13","author":"Piecuch","year":"2025","journal-title":"Pharm (Basel)"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5637685","article-title":"Exaggerated IL-15 and altered expression of foxp3+ cell-derived cytokines contribute to enhanced colitis in Nlrp3-\/- mice","volume":"2016","author":"Hirota","year":"2016","journal-title":"Mediators Inflammation"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.886213","article-title":"Selective targeting of IL-15Ralpha is sufficient to reduce inflammation","volume":"13","author":"Meghnem","year":"2022","journal-title":"Front Immunol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.580467","article-title":"Metabolic regulation of group 3 innate lymphoid cells and their role in inflammatory bowel disease","volume":"11","author":"Song","year":"2020","journal-title":"Front Immunol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s11882-016-0652-3","article-title":"Dysregulation of group 3 innate lymphoid cells in the pathogenesis of inflammatory bowel disease","volume":"16","author":"Forkel","year":"2016","journal-title":"Curr Allergy Asthma Rep"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.017","article-title":"Regulated expression of nuclear receptor RORgammat confers distinct functional fates to NK cell receptor-expressing RORgammat(+) innate lymphocytes","volume":"33","author":"Vonarbourg","year":"2010","journal-title":"Immunity"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115793","article-title":"RORgammat is crucial for gut homeostasis by regulating the expression of HB-EGF rather than IL-22 in activated ILC3s","volume":"44","author":"Li","year":"2025","journal-title":"Cell Rep"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121588","article-title":"Retinoic acid expression associates with enhanced IL-22 production by \u03b3\u03b4 T cells and innate lymphoid cells and attenuation of intestinal inflammation","volume":"210","author":"Mielke","year":"2013","journal-title":"J Exp Med"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.009","article-title":"Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut","volume":"43","author":"Kim","year":"2015","journal-title":"Immunity"},{"key":"B121","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.immuni.2011.11.011","article-title":"The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells","volume":"36","author":"Qiu","year":"2012","journal-title":"Immunity"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214914","article-title":"Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles","volume":"334","author":"Kiss","year":"2011","journal-title":"Science"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/nature21080","article-title":"Feedback control of AHR signalling regulates intestinal immunity","volume":"542","author":"Schiering","year":"2017","journal-title":"Nature"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.3280247","article-title":"Vitamin D\/vitamin D receptor signaling is required for normal development and function of group 3 innate lymphoid cells in the gut","volume":"17","author":"He","year":"2019","journal-title":"iScience"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.01.045","article-title":"Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells","volume":"141","author":"Konya","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1038\/nri1001","article-title":"Interleukin-12 and the regulation of innate resistance and adaptive immunity","volume":"3","author":"Trinchieri","year":"2003","journal-title":"Nat Rev Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1891742\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:18:04Z","timestamp":1788787084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1891742\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":126,"alternative-id":["10.3389\/fimmu.2026.1891742"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1891742","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"1891742"}}