{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T09:46:13Z","timestamp":1782726373718,"version":"3.54.5"},"reference-count":101,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82400472"],"award-info":[{"award-number":["82400472"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2025C1205"],"award-info":[{"award-number":["2025C1205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anhui Hongde Shanyi Medical Foundation","award":["KYZX2024016"],"award-info":[{"award-number":["KYZX2024016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gut, whose pathogenesis is closely related to immune dysregulation. Regulatory T cells (Tregs), as a key cell population maintaining intestinal immune tolerance, exhibit not only reduced frequency but, more critically, profound functional deficiencies, including the generation of proinflammatory ex-Tregs, and loss of lineage stability in the inflamed gut microenvironment of IBD. This review systematically delineates the sophisticated biological characteristics of Tregs, with a particular focus on the epigenetic and metabolic checkpoints that govern their stability. We critically summarize the aberrant changes of Tregs in IBD, emphasizing mechanisms such as inflammatory cytokine-induced Treg plasticity (eg Th1-like or Th17-like conversion) and microbiota-metabolite axis-mediated functional modulation. Furthermore, we provide an in-depth analysis of emerging therapeutic strategies aimed at restoring Treg suppressive capacity, including selective cytokine therapy (eg low-dose\/engineered IL-2), adoptive transfer of engineered antigen-specific Tregs (including CAR-Tregs), microbiome\/dietary interventions, and pharmacological modulation of Treg differentiation. We also discuss the disrupted crosstalk between Tregs and other innate and adaptive immune cells within the IBD milieu. Finally, this review highlights how cutting-edge technologies like single-cell multiomics and spatial transcriptomics are delineating the heterogeneous landscape and uncovering novel, disease-specific Treg subpopulations, thereby paving the way for precise Treg-targeting therapies. Unlike previous reviews that broadly catalog Treg abnormalities, this review offers a refined conceptual framework centered on the critical distinction between lineage-defective ex-Tregs and exhausted effector Tregs, and integrates recent multiomics insights to redefine Treg functional failure in IBD.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag067","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:47:32Z","timestamp":1779882452000},"source":"Crossref","is-referenced-by-count":0,"title":["Beyond suppression: the plasticity, dysfunction, and therapeutic reprogramming of regulatory T cells in inflammatory bowel disease"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6846-4034","authenticated-orcid":false,"given":"Yunting","family":"Shao","sequence":"first","affiliation":[{"name":"School of Medicine, Liaocheng University , No. 1, Hunan Road, Dongchangfu District, Liaocheng, Shandong Province 252000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0621-0434","authenticated-orcid":false,"given":"Shaochen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Chuzhou Integrated Traditional Chinese and Western Medicine Hospital , No. 788, Huifeng East Road, Nanqiao District, Chuzhou, Anhui Province 239000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7954-1670","authenticated-orcid":false,"given":"Mengjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , No. 218, Jixi Road, Shushan District, Hefei, Anhui Province 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1990-7861","authenticated-orcid":false,"given":"Yuting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , No. 218, Jixi Road, Shushan District, Hefei, Anhui Province 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7738-9186","authenticated-orcid":false,"given":"Ziyue","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , No. 218, Jixi Road, Shushan District, Hefei, Anhui Province 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1297-5830","authenticated-orcid":false,"given":"Beibei","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , No. 218, Jixi Road, Shushan District, Hefei, Anhui Province 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3699-1125","authenticated-orcid":false,"given":"Jian","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University , No. 218, Jixi Road, Shushan District, Hefei, Anhui Province 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"2026062905114536000_qiag067-B1","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41579-025-01163-0","article-title":"Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities","volume":"23","author":"Iliev","year":"2025","journal-title":"Nat Rev Microbiol"},{"key":"2026062905114536000_qiag067-B2","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"2026062905114536000_qiag067-B3","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1002\/jcph.2189","article-title":"Personalized dosing of infliximab in patients with inflammatory bowel disease using a Bayesian approach: a next step in therapeutic drug monitoring","volume":"63","author":"Desai","year":"2023","journal-title":"J Clin Pharmacol"},{"key":"2026062905114536000_qiag067-B4","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1038\/s41467-024-45473-y","article-title":"Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17\/treg cell balance axis","volume":"15","author":"Jia","year":"2024","journal-title":"Nat Commun"},{"key":"2026062905114536000_qiag067-B5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20231244","article-title":"Treg-tissue cell interactions in repair and regeneration","volume":"221","author":"Loffredo","year":"2024","journal-title":"J Exp Med"},{"key":"2026062905114536000_qiag067-B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107184","article-title":"Metabolic regulation of the Th17\/Treg balance in inflammatory bowel disease","volume":"203","author":"Zhang","year":"2024","journal-title":"Pharmacol Res"},{"key":"2026062905114536000_qiag067-B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.911151","article-title":"Nature vs. nurture: FOXP3, genetics, and tissue environment shape Treg function","volume":"13","author":"Raugh","year":"2022","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B8","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1002\/eji.202049123","article-title":"Mechanisms of exTreg induction","volume":"51","author":"Saxena","year":"2021","journal-title":"Eur J Immunol"},{"key":"2026062905114536000_qiag067-B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1107397","article-title":"Identification of the novel FOXP3-dependent T(reg) cell transcription factor MEOX1 by high-dimensional analysis of human CD4(+) T cells","volume":"14","author":"Ba\u00dfler","year":"2023","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B10","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s12016-021-08866-1","article-title":"Improving the efficacy of regulatory T cell therapy","volume":"62","author":"Baeten","year":"2022","journal-title":"Clin Rev Allergy Immunol"},{"key":"2026062905114536000_qiag067-B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2021.101411","article-title":"Regulatory T cells induce transplant immune tolerance","volume":"67","author":"Lu","year":"2021","journal-title":"Transpl Immunol"},{"key":"2026062905114536000_qiag067-B12","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.immuni.2019.01.020","article-title":"Human FOXP3(+) regulatory T cell heterogeneity and function in autoimmunity and cancer","volume":"50","author":"Wing","year":"2019","journal-title":"Immunity"},{"key":"2026062905114536000_qiag067-B13","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1111\/imr.12160","article-title":"Ttregs, pTregs, and iTregs: similarities and differences","volume":"259","author":"Shevach","year":"2014","journal-title":"Immunol Rev"},{"key":"2026062905114536000_qiag067-B14","doi-asserted-by":"publisher","first-page":"5118","DOI":"10.1038\/s41467-022-32899-5","article-title":"PD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability","volume":"13","author":"Hurrell","year":"2022","journal-title":"Nat Commun"},{"key":"2026062905114536000_qiag067-B15","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.3390\/ijms21093347","article-title":"The role of TNFR2 and DR3 in the in vivo expansion of Tregs in T cell depleting transplantation regimens","volume":"21","author":"Rodriguez-Barbosa","year":"2020","journal-title":"Int J Mol Sci."},{"key":"2026062905114536000_qiag067-B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1560578","article-title":"The dual role of tissue regulatory T cells in tissue repair: return to homeostasis or fibrosis","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B17","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.ajt.2023.01.030","article-title":"Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severity","volume":"23","author":"Larson","year":"2023","journal-title":"Am J Transplant"},{"key":"2026062905114536000_qiag067-B18","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.smim.2011.10.002","article-title":"Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions","volume":"23","author":"Yamaguchi","year":"2011","journal-title":"Semin Immunol"},{"key":"2026062905114536000_qiag067-B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2023739118","article-title":"Treg-expressed CTLA-4 depletes CD80\/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells","volume":"118","author":"Tekguc","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026062905114536000_qiag067-B20","doi-asserted-by":"publisher","first-page":"14122","DOI":"10.1073\/pnas.1204032109","article-title":"Activation of the noncanonical NF-kappaB pathway by HIV controls a dendritic cell immunoregulatory phenotype","volume":"109","author":"Manches","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026062905114536000_qiag067-B21","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.jgg.2024.09.014","article-title":"Improving regulatory T cell-based therapy: insights into post-translational modification regulation","volume":"52","author":"Wang","year":"2025","journal-title":"J Genet Genomics"},{"key":"2026062905114536000_qiag067-B22","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat1482","article-title":"Revisiting IL-2: biology and therapeutic prospects","volume":"3","author":"Abbas","year":"2018","journal-title":"Sci Immunol"},{"key":"2026062905114536000_qiag067-B23","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.jaci.2009.02.011","article-title":"IL-2- and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets","volume":"123","author":"Letourneau","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"2026062905114536000_qiag067-B24","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.3389\/fimmu.2019.02382","article-title":"Dynamic imprinting of the treg cell-specific epigenetic signature in developing thymic regulatory T cells","volume":"10","author":"Herppich","year":"2019","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1554028","article-title":"Iron and energy metabolic interactions in Treg-mediated immune regulation","volume":"16","author":"Savagner","year":"2025","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B26","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1080\/15548627.2019.1635384","article-title":"New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD","volume":"16","author":"Larabi","year":"2020","journal-title":"Autophagy"},{"key":"2026062905114536000_qiag067-B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1176016","article-title":"Feeding the gut microbiome: impact on multiple sclerosis","volume":"14","author":"Bronzini","year":"2023","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B28","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.4049\/jimmunol.1700604","article-title":"GPR81, a cell-surface receptor for lactate, regulates intestinal homeostasis and protects mice from experimental colitis","volume":"200","author":"Ranganathan","year":"2018","journal-title":"J Immunol"},{"key":"2026062905114536000_qiag067-B29","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.immuni.2018.12.015","article-title":"Microbiotas from humans with inflammatory bowel disease alter the balance of gut Th17 and ROR\u03b3t+ regulatory T cells and exacerbate colitis in mice","volume":"50","author":"Britton","year":"2019","journal-title":"Immunity"},{"key":"2026062905114536000_qiag067-B30","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1136\/gutjnl-2022-327075","article-title":"Autologous regulatory T-cell transfer in refractory ulcerative colitis with concomitant primary sclerosing cholangitis","volume":"72","author":"Voskens","year":"2023","journal-title":"Gut"},{"key":"2026062905114536000_qiag067-B31","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.3390\/ijms24032696","article-title":"CD4 T-cell subsets and the pathophysiology of inflammatory bowel disease","volume":"24","author":"Gomez-Bris","year":"2023","journal-title":"Int J Mol Sci."},{"key":"2026062905114536000_qiag067-B32","doi-asserted-by":"publisher","first-page":"178","DOI":"10.3389\/fimmu.2012.00178","article-title":"Multiple treg suppressive modules and their adaptability","volume":"3","author":"Wing","year":"2012","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B33","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/imr.13122","article-title":"Neuroinflammation: extinguishing a blaze of T cells","volume":"311","author":"Benallegue","year":"2022","journal-title":"Immunol Rev"},{"key":"2026062905114536000_qiag067-B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.929078","article-title":"Research progress on Th17 and T regulatory cells and their cytokines in regulating atherosclerosis","volume":"9","author":"Wang","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"2026062905114536000_qiag067-B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1058296","article-title":"Into the multi-omics era: progress of T cells profiling in the context of solid organ transplantation","volume":"14","author":"Zhi","year":"2023","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B36","doi-asserted-by":"publisher","first-page":"5229","DOI":"10.1158\/0008-5472.CAN-15-1798","article-title":"Lack of p53 augments antitumor functions in cytolytic T cells","volume":"76","author":"Banerjee","year":"2016","journal-title":"Cancer Res"},{"key":"2026062905114536000_qiag067-B37","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.3389\/fimmu.2019.03100","article-title":"Treg heterogeneity, function, and homeostasis","volume":"10","author":"Shevyrev","year":"2019","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B38","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41422-020-0324-7","article-title":"Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases","volume":"30","author":"Ohkura","year":"2020","journal-title":"Cell Res"},{"key":"2026062905114536000_qiag067-B39","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.3390\/ijms21093379","article-title":"Interplay between cytokine circuitry and transcriptional regulation shaping helper T cell pathogenicity and plasticity in inflammatory bowel disease","volume":"21","author":"Fu","year":"2020","journal-title":"Int J Mol Sci."},{"key":"2026062905114536000_qiag067-B40","doi-asserted-by":"publisher","first-page":"4736","DOI":"10.1038\/s41467-018-07254-2","article-title":"Inflammation-induced Id2 promotes plasticity in regulatory T cells","volume":"9","author":"Hwang","year":"2018","journal-title":"Nat Commun"},{"key":"2026062905114536000_qiag067-B41","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1053\/j.gastro.2011.09.015","article-title":"Gut-tropic T cells that express integrin alpha4beta7 and CCR9 are required for induction of oral immune tolerance in mice","volume":"141","author":"Cassani","year":"2011","journal-title":"Gastroenterology"},{"key":"2026062905114536000_qiag067-B42","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1136\/gutjnl-2023-330024","article-title":"Immunosuppressive CD29(+) Treg accumulation in the liver in mice on checkpoint inhibitor therapy","volume":"73","author":"Green","year":"2024","journal-title":"Gut"},{"key":"2026062905114536000_qiag067-B43","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2022.2108655","article-title":"The double-edged sword of probiotic supplementation on gut microbiota structure in Helicobacter pylori management","volume":"14","author":"Nabavi-Rad","year":"2022","journal-title":"Gut Microbes"},{"key":"2026062905114536000_qiag067-B44","doi-asserted-by":"publisher","first-page":"290","DOI":"10.3389\/fimmu.2016.00290","article-title":"Mucosal interactions between genetics, diet, and microbiome in inflammatory bowel disease","volume":"7","author":"Basson","year":"2016","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B45","doi-asserted-by":"publisher","first-page":"1565103","DOI":"10.3389\/fcimb.2025.1565103","article-title":"Progress on the mechanism of intestinal microbiota against colorectal cancer","volume":"15","author":"Xing","year":"2025","journal-title":"Front Cell Infect Microbiol"},{"key":"2026062905114536000_qiag067-B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118968","article-title":"Bile acids as signaling molecules in inflammatory bowel disease: implications for treatment strategies","volume":"337","author":"Ma","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"2026062905114536000_qiag067-B47","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo0183","article-title":"NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance","volume":"8","author":"Yang","year":"2022","journal-title":"Sci Adv"},{"key":"2026062905114536000_qiag067-B48","doi-asserted-by":"publisher","first-page":"3981","DOI":"10.1016\/j.cell.2021.05.028","article-title":"A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells","volume":"184","author":"Wong","year":"2021","journal-title":"Cell"},{"key":"2026062905114536000_qiag067-B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1387975","article-title":"Regulation of Treg cells by cytokine signaling and co-stimulatory molecules","volume":"15","author":"Zong","year":"2024","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136485","article-title":"Human blood and mucosal regulatory T cells express activation markers and inhibitory receptors in inflammatory bowel disease","volume":"10","author":"Lord","year":"2015","journal-title":"PLoS One"},{"key":"2026062905114536000_qiag067-B51","doi-asserted-by":"publisher","first-page":"5683","DOI":"10.1038\/s41598-022-09700-0","article-title":"Intestinal bacteria flora changes in patients with Mycoplasma pneumoniae pneumonia with or without wheezing","volume":"12","author":"Jiang","year":"2022","journal-title":"Sci Rep"},{"key":"2026062905114536000_qiag067-B52","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13045-022-01322-3","article-title":"Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity","volume":"15","author":"Yan","year":"2022","journal-title":"J Hematol Oncol"},{"key":"2026062905114536000_qiag067-B53","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.3390\/cancers12071888","article-title":"Relevance of regulatory T cells during colorectal cancer development","volume":"12","author":"Olguin","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2026062905114536000_qiag067-B54","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.729084","article-title":"Lymphocytes: versatile participants in acute kidney injury and progression to chronic kidney disease","volume":"12","author":"Cao","year":"2021","journal-title":"Front Physiol"},{"key":"2026062905114536000_qiag067-B55","doi-asserted-by":"publisher","DOI":"10.1155\/mi\/6733477","article-title":"Unraveling the gut-liver-brain axis: microbiome, inflammation, and emerging therapeutic approaches","volume":"2025","author":"Aghara","year":"2025","journal-title":"Mediators Inflamm"},{"key":"2026062905114536000_qiag067-B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1667053","article-title":"Opportunities and challenges harnessing antigen-specific CD4+ regulatory T cells in inflammatory bowel disease","volume":"16","author":"Kummel","year":"2025","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B57","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/mi.2017.64","article-title":"Regulatory T cells with superior immunosuppressive capacity emigrate from the inflamed colon to draining lymph nodes","volume":"11","author":"Nakanishi","year":"2018","journal-title":"Mucosal Immunol"},{"key":"2026062905114536000_qiag067-B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.554880","article-title":"Innate lymphoid cells in Crohn's disease","volume":"11","author":"Wu","year":"2020","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B59","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jcmgh.2017.03.010","article-title":"Induction of colonic regulatory T cells by mesalamine by activating the aryl hydrocarbon receptor","volume":"4","author":"Oh-Oka","year":"2017","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"2026062905114536000_qiag067-B60","doi-asserted-by":"publisher","first-page":"114458","DOI":"10.1016\/j.celrep.2024.114458","article-title":"SWI\/SNF chromatin remodeling factor BAF60b restrains inflammatory diseases by affecting regulatory T cell migration","volume":"43","author":"Liu","year":"2024","journal-title":"Cell Rep"},{"key":"2026062905114536000_qiag067-B61","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.cell.2015.08.021","article-title":"A distinct function of regulatory T cells in tissue protection","volume":"162","author":"Arpaia","year":"2015","journal-title":"Cell"},{"key":"2026062905114536000_qiag067-B62","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00535-015-1098-4","article-title":"Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease","volume":"51","author":"Okamoto","year":"2016","journal-title":"J Gastroenterol"},{"key":"2026062905114536000_qiag067-B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1199422","article-title":"Complex interactions of cellular players in chronic graft-versus-host disease","volume":"14","author":"Gail","year":"2023","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B64","doi-asserted-by":"publisher","first-page":"8924","DOI":"10.7150\/thno.47118","article-title":"An emerging role of regulatory T-cells in cardiovascular repair and regeneration","volume":"10","author":"Fung","year":"2020","journal-title":"Theranostics"},{"key":"2026062905114536000_qiag067-B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2024.103181","article-title":"A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease","volume":"144","author":"Saviano","year":"2024","journal-title":"J Autoimmun"},{"key":"2026062905114536000_qiag067-B66","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221435","article-title":"Emerging functions of tissue-resident eosinophils","volume":"220","author":"Gurtner","year":"2023","journal-title":"J Exp Med"},{"key":"2026062905114536000_qiag067-B67","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/s41586-022-05089-y","article-title":"A ROR\u03b3t+ cell instructs gut microbiota-specific T(reg) cell differentiation","volume":"610","author":"Kedmi","year":"2022","journal-title":"Nature"},{"key":"2026062905114536000_qiag067-B68","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1038\/s41467-024-45870-3","article-title":"IKK2 controls the inflammatory potential of tissue-resident regulatory T cells in a murine gain of function model","volume":"15","author":"Cardinez","year":"2024","journal-title":"Nat Commun"},{"key":"2026062905114536000_qiag067-B69","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1186\/s12967-025-06413-6","article-title":"Treg and intestinal myofibroblasts-derived amphiregulin induced by TGF-beta mediates intestinal fibrosis in Crohn's disease","volume":"23","author":"Wang","year":"2025","journal-title":"J Transl Med."},{"key":"2026062905114536000_qiag067-B70","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.immuni.2024.01.009","article-title":"Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis","volume":"57","author":"Savage","year":"2024","journal-title":"Immunity"},{"key":"2026062905114536000_qiag067-B71","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1053\/j.gastro.2011.02.059","article-title":"Human colonic myofibroblasts promote expansion of CD4+ CD25high Foxp3+ regulatory T cells","volume":"140","author":"Pinchuk","year":"2011","journal-title":"Gastroenterology"},{"key":"2026062905114536000_qiag067-B72","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1016\/j.immuni.2024.07.016","article-title":"Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics","volume":"57","author":"Raeber","year":"2024","journal-title":"Immunity"},{"key":"2026062905114536000_qiag067-B73","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1136\/annrheumdis-2018-214229","article-title":"Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial","volume":"78","author":"Rosenzwajg","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"2026062905114536000_qiag067-B74","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1291724","article-title":"The interplay between the microbiota, diet and T regulatory cells in the preservation of the gut barrier in inflammatory bowel disease","volume":"14","author":"Prame Kumar","year":"2023","journal-title":"Front Microbiol"},{"key":"2026062905114536000_qiag067-B75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01106","article-title":"Defining the threshold IL-2 signal required for induction of selective Treg cell responses using engineered IL-2 muteins","volume":"11","author":"Ghelani","year":"2020","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B76","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/mi.2015.74","article-title":"Foxp3(+) T cells expressing ROR\u03b3t represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation","volume":"9","author":"Yang","year":"2016","journal-title":"Mucosal Immunol"},{"key":"2026062905114536000_qiag067-B77","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41420-021-00534-9","article-title":"MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice","volume":"7","author":"Lu","year":"2021","journal-title":"Cell Death Discov"},{"key":"2026062905114536000_qiag067-B78","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae135","article-title":"IL23R-specific CAR Tregs for the treatment of Crohn's disease","volume":"19","author":"Cui","year":"2025","journal-title":"J Crohns Colitis"},{"key":"2026062905114536000_qiag067-B79","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2523815","article-title":"Microbiota-dependent metabolites\u2014new engine for T cell warriors","volume":"17","author":"Tang","year":"2025","journal-title":"Gut Microbes"},{"key":"2026062905114536000_qiag067-B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.620170","article-title":"Intestinal bacteria encapsulated by biomaterials enhance immunotherapy","volume":"11","author":"Liu","year":"2020","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B81","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1186\/s12951-025-03702-6","article-title":"Lactobacillus johnsonii-derived extracellular vesicles restore mucosal immunity via taurine-linked Th17\/Treg and IgA\/IgG regulation in colitis","volume":"23","author":"Zhao","year":"2025","journal-title":"J Nanobiotechnol"},{"key":"2026062905114536000_qiag067-B82","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/JLB.3A1218-476RR","article-title":"Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells","volume":"106","author":"Alrafas","year":"2019","journal-title":"J Leukoc Biol"},{"key":"2026062905114536000_qiag067-B83","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1053\/j.gastro.2024.01.007","article-title":"The FOXP3(+) pro-inflammatory T cell: a potential therapeutic target in Crohn's disease","volume":"166","author":"Kosinsky","year":"2024","journal-title":"Gastroenterology"},{"key":"2026062905114536000_qiag067-B84","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.mucimm.2024.12.014","article-title":"Targeting the EP2 receptor ameliorates inflammatory bowel disease in mice by enhancing the immunosuppressive activity of T(reg) cells","volume":"18","author":"Wang","year":"2025","journal-title":"Mucosal Immunol"},{"key":"2026062905114536000_qiag067-B85","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/s41385-020-00354-7","article-title":"Dopaminergic signalling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation","volume":"14","author":"Ugalde","year":"2021","journal-title":"Mucosal Immunol"},{"key":"2026062905114536000_qiag067-B86","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1038\/s41590-025-02166-y","article-title":"Succinate drives gut inflammation by promoting FOXP3 degradation through a molecular switch","volume":"26","author":"Wang","year":"2025","journal-title":"Nat Immunol"},{"key":"2026062905114536000_qiag067-B87","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.adg0699","article-title":"Multivalent, asymmetric IL-2-Fc fusions show enhanced selectivity for regulatory T cells","volume":"16","author":"Orcutt-Jahns","year":"2023","journal-title":"Sci Signal"},{"key":"2026062905114536000_qiag067-B88","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.jare.2025.08.017","article-title":"Microbiome-metabolome generated bile acids gatekeep infliximab efficacy in Crohn's disease by licensing M1 suppression and Treg dominance","volume":"83","author":"Liu","year":"2026","journal-title":"J Adv Res"},{"key":"2026062905114536000_qiag067-B89","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1179311","article-title":"Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis","volume":"14","author":"Seal","year":"2023","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B90","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.22038\/IJBMS.2024.74640.16209","article-title":"Co-administration of 1,25-dihydroxyvitamin D3 and infliximab improves colitis in mice by modulating Treg differentiation","volume":"27","author":"Hu","year":"2024","journal-title":"Iran J Basic Med Sci"},{"key":"2026062905114536000_qiag067-B91","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13073-020-00756-z","article-title":"Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis","volume":"12","author":"Trzupek","year":"2020","journal-title":"Genome Med"},{"key":"2026062905114536000_qiag067-B92","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/s41577-023-00836-2","article-title":"Locally sourced: site-specific immune barriers to metastasis","volume":"23","author":"Correia","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"2026062905114536000_qiag067-B93","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41573-019-0041-4","article-title":"Next-generation regulatory T cell therapy","volume":"18","author":"Ferreira","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"2026062905114536000_qiag067-B94","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2208436119","article-title":"Biosensors for inflammation as a strategy to engineer regulatory T cells for cell therapy","volume":"119","author":"Bittner","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026062905114536000_qiag067-B95","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1166135","article-title":"Opportunities for Treg cell therapy for the treatment of human disease","volume":"14","author":"Bluestone","year":"2023","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B96","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/mi.2013.73","article-title":"New targets for mucosal healing and therapy in inflammatory bowel diseases","volume":"7","author":"Neurath","year":"2014","journal-title":"Mucosal Immunol"},{"key":"2026062905114536000_qiag067-B97","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/ajt.14936","article-title":"Tailoring the homing capacity of human Tregs for directed migration to sites of Th1-inflammation or intestinal regions","volume":"19","author":"Hoeppli","year":"2019","journal-title":"Am J Transplant"},{"key":"2026062905114536000_qiag067-B98","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba1624","article-title":"Synthetic cytokine circuits that drive T cells into immune-excluded tumors","volume":"378","author":"Allen","year":"2022","journal-title":"Science"},{"key":"2026062905114536000_qiag067-B99","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1158\/2326-6066.CIR-21-0831","article-title":"Discovery of a conditionally activated IL-2 that promotes antitumor immunity and induces tumor regression","volume":"10","author":"Nirschl","year":"2022","journal-title":"Cancer Immunol Res"},{"key":"2026062905114536000_qiag067-B100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1612360","article-title":"Unlocking the therapeutic potential of thymus-isolated regulatory T cells","volume":"16","author":"Hu","year":"2025","journal-title":"Front Immunol"},{"key":"2026062905114536000_qiag067-B101","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1235889","article-title":"Monitoring regulatory T cells as a prognostic marker in lung transplantation","volume":"14","author":"Khan","year":"2023","journal-title":"Front Immunol"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/advance-article-pdf\/doi\/10.1093\/jleuko\/qiag067\/68413134\/qiag067.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/118\/6\/qiag067\/68413134\/qiag067.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/118\/6\/qiag067\/68413134\/qiag067.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T09:11:56Z","timestamp":1782724316000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/doi\/10.1093\/jleuko\/qiag067\/8696358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":101,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,8]]}},"URL":"https:\/\/doi.org\/10.1093\/jleuko\/qiag067","relation":{},"ISSN":["1938-3673"],"issn-type":[{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,5,28]]},"article-number":"qiag067"}}