{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:56:05Z","timestamp":1790520965432,"version":"4.1.0"},"reference-count":187,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 106-2320-B-400-032-MY3, MOST 106-2321-B-400-014, MOST 107-2321-B-400-016, MOST 108-2321-B-400-018"],"award-info":[{"award-number":["MOST 106-2320-B-400-032-MY3, MOST 106-2321-B-400-014, MOST 107-2321-B-400-016, MOST 108-2321-B-400-018"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-C108-007-008-S02, TSGH-C01-109013, VTA108-T-1-2, VTA109-T-1-1"],"award-info":[{"award-number":["TSGH-C108-007-008-S02, TSGH-C01-109013, VTA108-T-1-2, VTA109-T-1-1"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) is a chronic disorder manifested as Crohn\u2019s disease (CD) and ulcerative colitis (UC) characterized by intestinal inflammation and involves a dysregulated immune response against commensal microbiota through the activation of CD4 T helper cells. T helper cell differentiation to effector or regulatory phenotypes is controlled by cytokine networks and transcriptional regulators. Distinct polarized T helper cells are able to alter their phenotypes to adapt to diverse and fluctuating physiological environments. T helper cells exhibit intrinsic instability and flexibility to express cytokines of other lineages or transdifferentiate from one T helper cell type to another in response to various perturbations from physiological cytokine milieu as a means of promoting local immunity in response to injury or ensure tissue homeostasis. Furthermore, functional plasticity and diversity of T helper cells are associated with pathogenicity and are critical for immune homeostasis and prevention of autoimmunity. In this review, we provide deeper insights into the combinatorial extrinsic and intrinsic signals that control plasticity and transdifferentiation of T helper cells and also highlight the potential of exploiting the genetic reprogramming plasticity of T helper cells in the treatment of IBD.<\/jats:p>","DOI":"10.3390\/ijms21093379","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T10:01:18Z","timestamp":1589191278000},"page":"3379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Interplay between Cytokine Circuitry and Transcriptional Regulation Shaping Helper T Cell Pathogenicity and Plasticity in Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-6814","authenticated-orcid":false,"given":"Shin-Huei","family":"Fu","sequence":"first","affiliation":[{"name":"National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan"},{"name":"Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Wei","family":"Chien","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan"},{"name":"Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yuan","family":"Hsu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan"},{"name":"Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology, Taiwan International Graduate Program, Academia Sinica, No. 128, Academia Road, Section 2, Nankang, Taipei 11529, Taiwan"},{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Kang","family":"Sytwu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan"},{"name":"Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, No. 161, Section 6, Minquan East Road, Neihu District, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3748\/wjg.v20.i1.6","article-title":"Immunopathology of inflammatory bowel disease","volume":"20","author":"Wallace","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_2","first-page":"142","article-title":"The immunological basis of inflammatory bowel disease","volume":"60","author":"Cuvelier","year":"1997","journal-title":"Acta Gastroenterol. Belg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.cppeds.2014.10.003","article-title":"Inflammatory bowel disease: The classic gastrointestinal autoimmune disease","volume":"44","author":"Kaistha","year":"2014","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S2468-1253(16)30111-X","article-title":"Genetics of inflammatory bowel disease: Beyond NOD2","volume":"2","author":"Mirkov","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host\u2013microbe interactions have shaped the genetic architecture of inflammatory bowel disease","volume":"491","author":"Jostins","year":"2012","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations","volume":"47","author":"Liu","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ng.764","article-title":"Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47","volume":"43","author":"Anderson","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1136\/gut.2008.163667","article-title":"Crohn\u2019s disease: Th1, Th17 or both? The change of a paradigm: New immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn\u2019s disease","volume":"58","author":"Brand","year":"2009","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature22969","article-title":"Fine-mapping inflammatory bowel disease loci to single-variant resolution","volume":"547","author":"Huang","year":"2017","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.crohns.2014.01.003","article-title":"SMAD3 gene variant is a risk factor for recurrent surgery in patients with Crohn\u2019s disease","volume":"8","author":"Fowler","year":"2014","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1056\/NEJMoa1407250","article-title":"Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn\u2019s disease","volume":"372","author":"Monteleone","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.175","article-title":"Genome-wide association defines more than 30 distinct susceptibility loci for Crohn\u2019s disease","volume":"40","author":"Barrett","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/ng.221","article-title":"Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility","volume":"40","author":"Franke","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ng.717","article-title":"Genome-wide meta-analysis increases to 71 the number of confirmed Crohn\u2019s disease susceptibility loci","volume":"42","author":"Franke","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1056\/NEJMoa0907206","article-title":"Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor","volume":"361","author":"Glocker","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1159\/000228554","article-title":"Susceptibility genes and overall pathogenesis of inflammatory bowel disease: Where do we stand?","volume":"27","author":"Fiocchi","year":"2009","journal-title":"Dig. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.molmed.2009.03.002","article-title":"CD4 T-cell differentiation and inflammatory bowel disease","volume":"15","author":"Zenewicz","year":"2009","journal-title":"Trends Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1189\/jlb.0211099","article-title":"Mechanisms controlling Th17 cytokine expression and host defense","volume":"90","author":"McAleer","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1586\/eci.11.96","article-title":"Th17 cells: Interactions with predisposing factors in the immunopathogenesis of inflammatory bowel disease","volume":"8","author":"Raza","year":"2012","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/mi.2012.6","article-title":"RORgammat-dependent IL-17A-producing cells in the pathogenesis of intestinal inflammation","volume":"5","author":"Kanai","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cell.2009.09.033","article-title":"Induction of intestinal Th17 cells by segmented filamentous bacteria","volume":"139","author":"Ivanov","year":"2009","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/MRM.0b013e328348ce81","article-title":"Abnormal expansion of segmented filamentous bacteria in the gut: A role in pathogenesis of chronic inflammatory intestinal diseases?","volume":"22","author":"Bellavia","year":"2011","journal-title":"Rev. Med. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1097\/MIB.0000000000000811","article-title":"Profiles of Lamina Propria T Helper Cell Subsets Discriminate Between Ulcerative Colitis and Crohn\u2019s Disease","volume":"22","author":"Li","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/ibd.21905","article-title":"Compartmentalized expression of Th1 and Th17 cytokines in pediatric inflammatory bowel diseases","volume":"18","author":"Verdier","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_25","first-page":"967","article-title":"Multigene analysis unveils distinctive expression profiles of helper T-cell-related genes in the intestinal mucosa that discriminate between ulcerative colitis and Crohn\u2019s disease","volume":"20","author":"Iboshi","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1136\/gut.2009.182170","article-title":"Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease","volume":"58","author":"Rovedatti","year":"2009","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.advms.2016.09.001","article-title":"Cells of the innate and adaptive immunity and their interactions in inflammatory bowel disease","volume":"62","author":"Kmiec","year":"2017","journal-title":"Adv. Med. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cyto.2011.08.036","article-title":"TH1 and TH17 interactions in untreated inflamed mucosa of inflammatory bowel disease, and their potential to mediate the inflammation","volume":"56","author":"Olsen","year":"2011","journal-title":"Cytokine"},{"key":"ref_29","first-page":"1448","article-title":"Histopathological Features of Inflammatory Bowel Disease are Associated With Different CD4+ T Cell Subsets in Colonic Mucosal Lamina Propria","volume":"12","author":"Gui","year":"2018","journal-title":"J. Crohns Colitis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/01.MIB.0000197237.21387.mL","article-title":"TH1\/TH2-mediated colitis induced by adoptive transfer of CD4+CD45RBhigh T lymphocytes into nude mice","volume":"12","author":"Kanai","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3892\/mmr.2012.1111","article-title":"Cytokine expression and the role of Th17 cells in a mouse model of colitis","volume":"6","author":"He","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_32","first-page":"92","article-title":"Validation of a modified model of TNBS-induced colitis in rats. How to induce a chemical colitis in rats","volume":"86","author":"Tomasello","year":"2015","journal-title":"Acta Biomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ibd.20753","article-title":"Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis","volume":"15","author":"Alex","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1097\/00054725-200409000-00027","article-title":"Regulatory T cells: Peace keepers in the gut","volume":"10","author":"Allez","year":"2004","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fimmu.2013.00194","article-title":"CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology and Inflammatory Bowel Disease: Odd Couple or Axis of Evil?","volume":"4","author":"Lee","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10753-018-0875-7","article-title":"Pharmacological Evaluation of TAK-828F, a Novel Orally Available RORgammat Inverse Agonist, on Murine Colitis Model","volume":"42","author":"Igaki","year":"2019","journal-title":"Inflammation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1365-2567.2011.03520.x","article-title":"Regulation of CD4+ T-cell polarization by suppressor of cytokine signalling proteins","volume":"135","author":"Knosp","year":"2012","journal-title":"Immunology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000437106","article-title":"The IL-12\/23\/STAT Axis as a Therapeutic Target in Inflammatory Bowel Disease: Mechanisms and Evidence in Man","volume":"33","author":"Marafini","year":"2015","journal-title":"Dig. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1002\/eji.201646710","article-title":"The IL-10\/STAT3 axis: Contributions to immune tolerance by thymus and peripherally derived regulatory T-cells","volume":"47","author":"Schmetterer","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nature12199","article-title":"BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis","volume":"498","author":"Roychoudhuri","year":"2013","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/bfgp\/elt025","article-title":"Transcription factor interplay in T helper cell differentiation","volume":"12","author":"Evans","year":"2013","journal-title":"Brief. Funct. Genom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/eji.201847677","article-title":"Eomes controls the development of Th17-derived (non-classic) Th1 cells during chronic inflammation","volume":"49","author":"Mazzoni","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/eji.201847722","article-title":"Eomesodermin controls a unique differentiation program in human IL-10 and IFN-gamma coproducing regulatory T cells","volume":"49","author":"Gruarin","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/j.1365-2249.1995.tb03130.x","article-title":"Altered Th1\/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR)","volume":"101","author":"Niessner","year":"1995","journal-title":"Clin. Exp. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/mi.2007.17","article-title":"IL-21 comes of age as a regulator of effector T cells in the gut","volume":"1","author":"Fantini","year":"2008","journal-title":"Mucosal Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.cytogfr.2010.10.006","article-title":"Signal transduction pathways and transcriptional regulation in Th17 cell differentiation","volume":"21","author":"Hirahara","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Monteleone, I., Pallone, F., and Monteleone, G. (2011). Th17-related cytokines: New players in the control of chronic intestinal inflammation. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-122"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.3748\/wjg.14.4280","article-title":"Role of cytokines in inflammatory bowel disease","volume":"14","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_49","first-page":"e1177","article-title":"Crohn\u2019s Disease and Ulcerative Colitis Show Unique Cytokine Profiles","volume":"9","author":"Nemeth","year":"2017","journal-title":"Cureus"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/ibd.20148","article-title":"Il-6 signaling in inflammatory bowel disease: Pathophysiological role and clinical relevance","volume":"13","author":"Mudter","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.cytogfr.2014.07.017","article-title":"IL-12-and IL-23 in health and disease","volume":"25","author":"Croxford","year":"2014","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.biocel.2008.04.027","article-title":"Interleukin-23: Immunological roles and clinical implications","volume":"41","author":"Tan","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/j.1365-2796.2008.01950.x","article-title":"The Interleukin-23\/Interleukin-17 axis in intestinal inflammation","volume":"263","author":"Maloy","year":"2008","journal-title":"J. Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1002\/ibd.21248","article-title":"IL-23\/IL-17 axis in IBD","volume":"16","author":"Sarra","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1600-065X.2008.00705.x","article-title":"The interleukin-23 Axis in Intestinal Inflammation","volume":"226","author":"Ahern","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.med.60.051407.123757","article-title":"IL-23 and autoimmunity: New insights into the pathogenesis of inflammatory bowel disease","volume":"60","author":"Abraham","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.clim.2012.06.009","article-title":"Delivery of IL-12p40 ameliorates DSS-induced colitis by suppressing IL-17A expression and inflammation in the intestinal mucosa","volume":"144","author":"Kim","year":"2012","journal-title":"Clin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri3707","article-title":"The IL-23-IL-17 immune axis: From mechanisms to therapeutic testing","volume":"14","author":"Gaffen","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ejphar.2018.01.045","article-title":"Anti-IL-23 receptor monoclonal antibody prevents CD4(+) T cell-mediated colitis in association with decreased systemic Th1 and Th17 responses","volume":"824","author":"Imamura","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1097\/MIB.0000000000001270","article-title":"Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD","volume":"23","author":"Shouval","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0092-8674(93)80068-P","article-title":"Interleukin-10-deficient mice develop chronic enterocolitis","volume":"75","author":"Kuhn","year":"1993","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"G829","DOI":"10.1152\/ajpgi.2000.278.6.G829","article-title":"Lessons from genetically engineered animal models. XII. IL-10-deficient (IL-10(-\/-) mice and intestinal inflammation","volume":"278","author":"Rennick","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1177\/019262339902700124","article-title":"The Role of IL-10 in Inflammatory Bowel Disease: \u201cOf Mice and Men\u201d","volume":"27","author":"Leach","year":"1999","journal-title":"Toxicol. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/j.1365-2249.1995.tb03721.x","article-title":"Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD)","volume":"100","author":"Kucharzik","year":"1995","journal-title":"Clin. Exp. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0016-5085(95)90692-4","article-title":"Immunoregulatory Role of Interleukin 10 in Patients with Inflammatory Bowel Disease","volume":"108","author":"Schreiber","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1046\/j.1365-2249.2003.02268.x","article-title":"Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis","volume":"134","author":"Melgar","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.immuni.2008.02.017","article-title":"Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces","volume":"28","author":"Rubtsov","year":"2008","journal-title":"Immunity"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.it.2011.03.010","article-title":"The Th1 life cycle: Molecular control of IFN-gamma to IL-10 switching","volume":"32","author":"Cope","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1002\/ibd.22929","article-title":"Healing of intestinal inflammation by IL-22","volume":"18","author":"Mizoguchi","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/ni.2025","article-title":"Border patrol: Regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22","volume":"12","author":"Sonnenberg","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/mi.2013.31","article-title":"IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue","volume":"7","author":"Leung","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1007\/s10620-017-4596-9","article-title":"Crossover Subsets of CD4(+) T Lymphocytes in the Intestinal Lamina Propria of Patients with Crohn\u2019s Disease and Ulcerative Colitis","volume":"62","author":"Li","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/B978-0-12-381300-8.00005-8","article-title":"The many face-lifts of CD4 T helper cells","volume":"107","author":"Mucida","year":"2010","journal-title":"Adv. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/B978-0-12-387664-5.00005-4","article-title":"T helper cell differentiation more than just cytokines","volume":"109","author":"Zygmunt","year":"2011","journal-title":"Adv. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2174\/156652412800620066","article-title":"Th17-related cytokines in inflammatory bowel diseases: Friends or foes?","volume":"12","author":"Monteleone","year":"2012","journal-title":"Curr. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.immuni.2009.05.012","article-title":"Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose","volume":"31","author":"Saraiva","year":"2009","journal-title":"Immunity"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/eji.200636385","article-title":"Expression of IL-10 in Th memory lymphocytes is conditional on IL-12 or IL-4, unless the IL-10 gene is imprinted by GATA-3","volume":"37","author":"Chang","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.4049\/jimmunol.0900123","article-title":"c-Maf regulates IL-10 expression during Th17 polarization","volume":"182","author":"Xu","year":"2009","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1084\/jem.20131548","article-title":"Role of Blimp-1 in programing Th effector cells into IL-10 producers","volume":"211","author":"Neumann","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nature09447","article-title":"Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling","volume":"467","author":"Ghoreschi","year":"2010","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1084\/jem.20030917","article-title":"Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis","volume":"198","author":"Kitani","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41590-019-0316-2","article-title":"c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host-microbiota homeostasis","volume":"20","author":"Neumann","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"797","DOI":"10.4049\/jimmunol.0901233","article-title":"Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells","volume":"183","author":"Pot","year":"2009","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/ni.1912","article-title":"The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27","volume":"11","author":"Apetoh","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41590-018-0083-5","article-title":"c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells","volume":"19","author":"Luisier","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/ni1320","article-title":"Transcriptional repressor Blimp-1 regulates T cell homeostasis and function","volume":"7","author":"Martins","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ni.1996","article-title":"CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs","volume":"12","author":"Sun","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1002\/eji.201242942","article-title":"Egr-2 transcription factor is required for Blimp-1-mediated IL-10 production in IL-27-stimulated CD4+ T cells","volume":"43","author":"Iwasaki","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/ni.2006","article-title":"The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells","volume":"12","author":"Cretney","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1172\/JCI66108","article-title":"Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1","volume":"124","author":"Parish","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nri2711","article-title":"The regulation of IL-10 production by immune cells","volume":"10","author":"Saraiva","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/ni1537","article-title":"Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10","volume":"8","author":"Stumhofer","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.immuni.2012.11.003","article-title":"Interleukin-27: Balancing protective and pathological immunity","volume":"37","author":"Hunter","year":"2012","journal-title":"Immunity"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S1074-7613(03)00300-5","article-title":"The IL-27R (WSX-1) Is Required to Suppress T Cell Hyperactivity During Infection","volume":"19","author":"Villarino","year":"2003","journal-title":"Immunity"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1073\/pnas.0712102105","article-title":"Notch regulates IL-10 production by T helper 1 cells","volume":"105","author":"Rutz","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"550","DOI":"10.4049\/jimmunol.0903152","article-title":"Cutting edge: Plasmacytoid dendritic cells induce IL-10 production in T cells via the Delta-like-4\/Notch axis","volume":"184","author":"Kassner","year":"2010","journal-title":"J. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"eaah7152","DOI":"10.1126\/sciimmunol.aah7152","article-title":"Eomesodermin promotes the development of type 1 regulatory T (TR1) cells","volume":"2","author":"Zhang","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.clim.2015.11.011","article-title":"IL-10\/IFNgamma co-expressing CD4(+) T cells induced by IL-10 DC display a regulatory gene profile and downmodulate T cell responses","volume":"162","author":"Boks","year":"2016","journal-title":"Clin. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/j.jaci.2017.12.984","article-title":"Intestinal IFN-gamma-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease","volume":"142","author":"Alfen","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1053\/j.gastro.2019.09.002","article-title":"Suppressive and Gut-Reparative Functions of Human Type 1 T Regulatory Cells","volume":"157","author":"Cook","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1038\/s41390-019-0662-7","article-title":"Increased frequency of regulatory T cells in pediatric inflammatory bowel disease at diagnosis: A compensative role?","volume":"87","author":"Vitale","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"G568","DOI":"10.1152\/ajpgi.00329.2010","article-title":"Treatment with IL-27 attenuates experimental colitis through the suppression of the development of IL-17-producing T helper cells","volume":"300","author":"Sasaoka","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1038\/ncomms4199","article-title":"TNF-\u03b1 blockade induces IL-10 expression in human CD4+ T cells","volume":"5","author":"Evans","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3389\/fimmu.2017.00157","article-title":"TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells","volume":"8","author":"Roberts","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1136\/gutjnl-2013-306585","article-title":"Targeting tumour necrosis factor receptor 1 assembly reverses Th17-mediated colitis through boosting a Th2 response","volume":"64","author":"Fu","year":"2015","journal-title":"Gut"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.smim.2013.10.021","article-title":"Identity crisis of Th17 cells: Many forms, many functions, many questions","volume":"25","author":"Sundrud","year":"2013","journal-title":"Semin. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2174\/187152808785748155","article-title":"Therapeutic benefits of regulating inflammation in autoimmunity","volume":"7","author":"Nikoopour","year":"2008","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/s41590-018-0200-5","article-title":"An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells","volume":"19","author":"Aschenbrenner","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez, D., Flores-Santib\u00e1\u00f1ez, F., Neira, J., Osorio-Barrios, F., Tej\u00f3n, G., Nu\u00f1ez, S., Hidalgo, Y., Fuenzalida, M.J., Meza, D., and Ureta, G. (2016). Purinergic Signaling as a Regulator of Th17 Cell Plasticity. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157889"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.bbrc.2019.01.123","article-title":"Ascl2 facilitates IL-10 production in Th17 cells to restrain their pathogenicity in inflammatory bowel disease","volume":"510","author":"Yi","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.bbrc.2019.11.122","article-title":"Sauchinone ameliorates intestinal inflammation and promotes Th17 cell production of IL-10 via Blimp-1","volume":"522","author":"Xiao","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/JLB.1RI0418-152RR","article-title":"Transcriptional regulation of CD4+ TH cells that mediate tissue inflammation","volume":"104","author":"Loo","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.immuni.2008.12.012","article-title":"Programming perpetual T helper cell plasticity","volume":"30","author":"Rowell","year":"2009","journal-title":"Immunity"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.immuni.2008.12.009","article-title":"Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells","volume":"30","author":"Wei","year":"2009","journal-title":"Immunity"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.immuni.2008.11.005","article-title":"Late developmental plasticity in the T helper 17 lineage","volume":"30","author":"Lee","year":"2009","journal-title":"Immunity"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Tindemans, I., Joosse, M.E., and Samsom, J.N. (2020). Dissecting the Heterogeneity in T-Cell Mediated Inflammation in IBD. Cells, 9.","DOI":"10.3390\/cells9010110"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.cyto.2013.04.015","article-title":"Superantigens induce IL-17 production from polarized Th1 clones","volume":"63","author":"Yomogida","year":"2013","journal-title":"Cytokine"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5615","DOI":"10.4049\/jimmunol.1101058","article-title":"Human Th1 and Th17 cells exhibit epigenetic stability at signature cytokine and transcription factor loci","volume":"187","author":"Cohen","year":"2011","journal-title":"J. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.immuni.2015.02.003","article-title":"Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program","volume":"42","author":"Brown","year":"2015","journal-title":"Immunity"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1002\/eji.201444726","article-title":"TGF-beta converts Th1 cells into Th17 cells through stimulation of Runx1 expression","volume":"45","author":"Liu","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1182\/blood-2015-05-646182","article-title":"SUMOylation-disrupting WAS mutation converts WASp from a transcriptional activator to a repressor of NF-\u03baB response genes in T cells","volume":"126","author":"Sarkar","year":"2015","journal-title":"Blood"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"30","DOI":"10.4049\/jimmunol.0903412","article-title":"Cutting edge: The Th1 response inhibits the generation of peripheral regulatory T cells","volume":"184","author":"Caretto","year":"2010","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jaut.2012.06.004","article-title":"Identification of a human Th1-like IFNgamma-secreting Treg subtype deriving from effector T cells","volume":"39","author":"Venigalla","year":"2012","journal-title":"J. Autoimmun."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s10620-010-1286-2","article-title":"CD4+CD25+ regulatory T cells suppress Th17-responses in an experimental colitis model","volume":"56","author":"Ogino","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s10875-009-9345-1","article-title":"Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease","volume":"30","author":"Mabarrack","year":"2010","journal-title":"J. Clin. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.12669\/pjms.325.10902","article-title":"Expression of Treg\/Th17 cells as well as related cytokines in patients with inflammatory bowel disease","volume":"32","author":"Geng","year":"2016","journal-title":"Pak. J. Med. Sci."},{"key":"ref_127","first-page":"4","article-title":"Serum IL-6, IL-23 profile and Treg\/Th17 peripheral cell populations in pediatric patients with inflammatory bowel disease","volume":"72","author":"Zhu","year":"2017","journal-title":"Pharmazie"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1189\/jlb.3HI0614-303R","article-title":"Chemokine receptor CCR7 regulates the intestinal TH1\/TH17\/Treg balance during Crohn\u2019s-like murine ileitis","volume":"97","author":"McNamee","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.immuni.2008.05.007","article-title":"Molecular antagonism and plasticity of regulatory and inflammatory T cell programs","volume":"29","author":"Yang","year":"2008","journal-title":"Immunity"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1189\/jlb.0109006","article-title":"All-trans retinoic acid down-regulates inflammatory responses by shifting the Treg\/Th17 profile in human ulcerative and murine colitis","volume":"86","author":"Bai","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"70","DOI":"10.18632\/oncotarget.13783","article-title":"High salt diet stimulates gut Th17 response and exacerbates TNBS-induced colitis in mice","volume":"8","author":"Wei","year":"2017","journal-title":"Oncotarget"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.immuni.2009.08.020","article-title":"The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses","volume":"31","author":"Rakotobe","year":"2009","journal-title":"Immunity"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7931","DOI":"10.1007\/s00253-019-10094-9","article-title":"Preventative delivery of IL-35 by Lactococcus lactis ameliorates DSS-induced colitis in mice","volume":"103","author":"Wang","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1189\/jlb.1011518","article-title":"HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis","volume":"91","author":"Higashiyama","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"26847","DOI":"10.1074\/jbc.M114.590554","article-title":"Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17\/Treg cell balance","volume":"289","author":"Zhang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Hu, S., Chen, M., Wang, Y., Wang, Z., Pei, Y., Fan, R., Liu, X., Wang, L., Zhou, J., and Zheng, S. (2016). mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1\/TH17\/Treg Profile. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159758"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"10888","DOI":"10.1038\/ncomms10888","article-title":"IL-15-dependent balance between Foxp3 and RORgammat expression impacts inflammatory bowel disease","volume":"7","author":"Tosiek","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"6309219","DOI":"10.1155\/2016\/6309219","article-title":"Balancing Inflammation: The Link between Th17 and Regulatory T Cells","volume":"2016","author":"Diller","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1182\/blood-2012-09-378653","article-title":"Essentials of Th17 cell commitment and plasticity","volume":"121","author":"Muranski","year":"2013","journal-title":"Blood"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/imr.12035","article-title":"The Th17 family: Flexibility follows function","volume":"252","author":"Basu","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.coi.2009.05.021","article-title":"Developmental plasticity of Th17 and Treg cells","volume":"21","author":"Lee","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jaut.2017.12.004","article-title":"Th17 plasticity and its relevance to inflammatory bowel disease","volume":"87","author":"Ueno","year":"2018","journal-title":"J. Autoimmun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.3748\/wjg.v21.i43.12283","article-title":"Th17 plasticity and its changes associated with inflammatory bowel disease","volume":"21","author":"Ueno","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3109\/08830185.2013.843983","article-title":"The Th17 cell population and the immune homeostasis of the gastrointestinal tract","volume":"32","author":"Rossi","year":"2013","journal-title":"Int. Rev. Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.coph.2014.06.004","article-title":"Th17 plasticity: Pathophysiology and treatment of chronic inflammatory disorders","volume":"17","author":"Cosmi","year":"2014","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.molimm.2018.11.015","article-title":"A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders","volume":"105","author":"Kamali","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1097\/MIB.0000000000000210","article-title":"Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-gamma+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease","volume":"20","author":"Globig","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1053\/j.gastro.2016.05.050","article-title":"Commensal-Specific CD4(+) Cells From Patients With Crohn\u2019s Disease Have a T-Helper 17 Inflammatory Profile","volume":"151","author":"Dotti","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1002\/eji.201242648","article-title":"Distinctive features of classic and nonclassic (Th17 derived) human Th1 cells","volume":"42","author":"Maggi","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.it.2012.05.004","article-title":"Defining the human T helper 17 cell phenotype","volume":"33","author":"Annunziato","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000343467","article-title":"CD4+CD161+ T lymphocytes infiltrate Crohn\u2019s disease-associated perianal fistulas and are reduced by anti-TNF-alpha local therapy","volume":"161","author":"Maggi","year":"2013","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.4049\/jimmunol.0803931","article-title":"Cutting edge: In vitro generated Th17 cells maintain their cytokine expression program in normal but not lymphopenic hosts","volume":"182","author":"Nurieva","year":"2009","journal-title":"J. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1002\/eji.201040755","article-title":"Genetic proof for the transient nature of the Th17 phenotype","volume":"40","author":"Kurschus","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.imbio.2011.07.032","article-title":"IL-12 inhibits the TGF-beta-dependent T cell developmental programs and skews the TGF-beta-induced differentiation into a Th1-like direction","volume":"217","author":"Prochazkova","year":"2012","journal-title":"Immunobiology"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.immuni.2010.04.016","article-title":"Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage","volume":"32","author":"Mukasa","year":"2010","journal-title":"Immunity"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.4049\/jimmunol.1003216","article-title":"Epigenetic changes at Il12rb2 and Tbx21 in relation to plasticity behavior of Th17 cells","volume":"186","author":"Bending","year":"2011","journal-title":"J. Immunol."},{"key":"ref_157","first-page":"6","article-title":"The Role of interleukin-23 in Stability of in Vitro T helper-17 Cells","volume":"13","author":"Taherian","year":"2014","journal-title":"Iran. J. Allergy Asthma Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"7061","DOI":"10.1073\/pnas.1415675112","article-title":"Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis","volume":"112","author":"Harbour","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/mi.2013.11","article-title":"Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation","volume":"6","author":"Morrison","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.4049\/jimmunol.1600137","article-title":"Tbet or Continued RORgammat Expression Is Not Required for Th17-Associated Immunopathology","volume":"196","author":"Ferreira","year":"2016","journal-title":"J. Immunol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.3389\/fimmu.2019.01177","article-title":"Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn\u2019s Disease and Ulcerative Colitis Patients","volume":"10","author":"Bsat","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41467-017-00380-3","article-title":"JunB promotes Th17 cell identity and restrains alternative CD4(+) T-cell programs during inflammation","volume":"8","author":"Carr","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3389\/fimmu.2018.00184","article-title":"Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity","volume":"9","author":"Bhaskaran","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41586-018-0806-7","article-title":"Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity","volume":"565","author":"Karmaus","year":"2019","journal-title":"Nature"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"928461","DOI":"10.1155\/2014\/928461","article-title":"Role of Th17 Cells in the Pathogenesis of Human IBD","volume":"2014","author":"Galvez","year":"2014","journal-title":"ISRN Inflamm."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"6532","DOI":"10.1182\/blood-2010-11-317321","article-title":"Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells","volume":"117","author":"Hoechst","year":"2011","journal-title":"Blood"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.cell.2012.09.016","article-title":"A validated regulatory network for Th17 cell specification","volume":"151","author":"Ciofani","year":"2012","journal-title":"Cell"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Carbo, A., Hontecillas, R., Kronsteiner, B., Viladomiu, M., Pedragosa, M., Lu, P., Philipson, C.W., Hoops, S., Marathe, M., and Eubank, S. (2013). Systems modeling of molecular mechanisms controlling cytokine-driven CD4+ T cell differentiation and phenotype plasticity. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1003027"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/ni.2552","article-title":"Plasticity of Th17 cells in Peyer\u2019s patches is responsible for the induction of T cell-dependent IgA responses","volume":"14","author":"Hirota","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/imr.12175","article-title":"Lineage Stability and Phenotypic Plasticity of Foxp3\u207a Regulatory T Cells","volume":"259","author":"Hori","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1073\/pnas.0811556106","article-title":"Heterogeneity of natural Foxp3+ T cells: A committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity","volume":"106","author":"Komatsu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"7467","DOI":"10.4049\/jimmunol.1001519","article-title":"IL-17- and IFN-gamma-secreting Foxp3+ T cells infiltrate the target tissue in experimental autoimmunity","volume":"185","author":"Esposito","year":"2010","journal-title":"J. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/rheumatology\/keq328","article-title":"FoxP3+ CD4+ T cells in systemic autoimmune diseases: The delicate balance between true regulatory T cells and effector Th-17 cells","volume":"50","author":"Abdulahad","year":"2011","journal-title":"Rheumatology (Oxf.)"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1038\/mi.2008.51","article-title":"Regulatory T cells and the induction of IL-17","volume":"1","author":"Kitani","year":"2008","journal-title":"Mucosal Immunol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1053\/j.gastro.2010.12.002","article-title":"Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases","volume":"140","author":"Hovhannisyan","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1097\/MIB.0b013e3182a85709","article-title":"Increased prevalence of circulating novel IL-17 secreting Foxp3 expressing CD4+ T cells and defective suppressive function of circulating Foxp3+ regulatory cells support plasticity between Th17 and regulatory T cells in inflammatory bowel disease patients","volume":"19","author":"Ueno","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.12659\/MSM.896827","article-title":"Elevated IL-23R Expression and Foxp3+Rorgt+ Cells in Intestinal Mucosa During Acute and Chronic Colitis","volume":"22","author":"Yang","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_178","doi-asserted-by":"crossref","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 RORgammat(+) Regulatory T Cells and Exacerbate Colitis in Mice","volume":"50","author":"Britton","year":"2019","journal-title":"Immunity"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Yurchenko, E., Shio, M.T., Huang, T.C., Da Silva Martins, M., Szyf, M., Levings, M.K., Olivier, M., and Piccirillo, C.A. (2012). Inflammation-driven reprogramming of CD4+ Foxp3+ regulatory T cells into pathogenic Th1\/Th17 T effectors is abrogated by mTOR inhibition in vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035572"},{"key":"ref_180","doi-asserted-by":"crossref","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":"ref_181","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/eji.201040724","article-title":"Generation of human Th1-like regulatory CD4+ T cells by an intrinsic IFN-gamma-and T-bet-dependent pathway","volume":"41","author":"Zheng","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.3389\/fimmu.2019.02158","article-title":"Tbet Expression in Regulatory T Cells Is Required to Initiate Th1-Mediated Colitis","volume":"10","author":"Rizzo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1007\/s00018-017-2569-y","article-title":"Molecular mechanisms underlying Th1-like Treg generation and function","volume":"74","author":"Kitz","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1053\/j.gastro.2011.03.009","article-title":"Interleukin-12 converts Foxp3+ regulatory T cells to interferon-gamma-producing Foxp3+ T cells that inhibit colitis","volume":"140","author":"Feng","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4973964","DOI":"10.1155\/2018\/4973964","article-title":"DNA Methyltransferase Inhibition Promotes Th1 Polarization in Human CD4(+)CD25(high) FOXP3(+) Regulatory T Cells but Does Not Affect Their Suppressive Capacity","volume":"2018","author":"Landman","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1074\/jbc.M116.749663","article-title":"The Role of the Histone Methyltransferase Enhancer of Zeste Homolog 2 (EZH2) in the Pathobiological Mechanisms Underlying Inflammatory Bowel Disease (IBD)","volume":"292","author":"Sarmento","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fimmu.2018.00045","article-title":"GATA3, HDAC6, and BCL6 Regulate FOXP3+ Treg Plasticity and Determine Treg Conversion into Either Novel Antigen-Presenting Cell-Like Treg or Th1-Treg","volume":"9","author":"Xu","year":"2018","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3379\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:27:29Z","timestamp":1760174849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,11]]},"references-count":187,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijms21093379"],"URL":"https:\/\/doi.org\/10.3390\/ijms21093379","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,11]]}}}