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IBD is characterized by exacerbated innate and adaptive immunity in the gut in association with microbiota dysbiosis and the disruption of the intestinal barrier, resulting in increased bacterial exposure. In response to signals from microorganisms and damaged tissue, innate immune cells produce inflammatory cytokines and factors that stimulate T and B cells of the adaptive immune system, and a prominent characteristic of IBD patients is the accumulation of inflammatory T-cells and their proinflammatory-associated cytokines in intestinal tissue. Upon antigen recognition and activation, CD4 T-cells differentiate towards a range of distinct phenotypes: T helper(h)1, Th2, Th9, Th17, Th22, T follicular helper (Tfh), and several types of T-regulatory cells (Treg). T-cells are generated according to and adapt to microenvironmental conditions and participate in a complex network of interactions among other immune cells that modulate the further progression of IBD. This review examines the role of the CD4 T-cells most relevant to IBD, highlighting how these cells adapt to the environment and interact with other cell populations to promote or inhibit the development of IBD.<\/jats:p>","DOI":"10.3390\/ijms24032696","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:29:03Z","timestamp":1675218543000},"page":"2696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":247,"title":["CD4 T-Cell Subsets and the Pathophysiology of Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6665-7732","authenticated-orcid":false,"given":"Raquel","family":"Gomez-Bris","sequence":"first","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-4737","authenticated-orcid":false,"given":"Angela","family":"Saez","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Facultad de Ciencias Experimentales, Universidad Francisco de Vitoria (UFV), 28223 Pozuelo de Alarc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Herrero-Fernandez","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-5620","authenticated-orcid":false,"given":"Cristina","family":"Rius","sequence":"additional","affiliation":[{"name":"Department of History of Science and Information Science, School of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain"},{"name":"UISYS Research Unit, University of Valencia, 46010 Valencia, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Sanchez-Martinez","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1177-869X","authenticated-orcid":false,"given":"Jose M.","family":"Gonzalez-Granado","sequence":"additional","affiliation":[{"name":"LamImSys Lab, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Herrero-Fernandez, B., Gomez-Bris, R., Somovilla-Crespo, B., and Gonzalez-Granado, J.M. 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