{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:42:26Z","timestamp":1792104146174,"version":"4.4.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100001063","name":"Crohn\u2019s and Colitis Foundation of America","doi-asserted-by":"publisher","award":["347717"],"award-info":[{"award-number":["347717"]}],"id":[{"id":"10.13039\/100001063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurobehavioral disorders and brain abnormalities have been extensively reported in both Crohn\u2019s disease and ulcerative colitis patients. However, the mechanism causing neuropathological disorders in inflammatory bowel disease patients remains unknown. Studies have linked the Th17 subset of CD4+ T cells to brain diseases associated with neuroinflammation and cognitive impairment, including multiple sclerosis, ischemic brain injury, and Alzheimer\u2019s disease. To better understand how CD4+ T lymphocytes contribute to brain pathology in chronic intestinal inflammation, we investigated the development of brain inflammation in the T cell transfer model of chronic colitis. Our findings demonstrate that CD4+ T cells infiltrate the brain of colitic Rag1\u2212\/\u2212 mice in proportional levels to colitis severity. Colitic mice developed hypothalamic astrogliosis that correlated with neurobehavioral disorders. Moreover, the brain-infiltrating CD4+ T cells expressed Th17 cell transcription factor retinoic acid\u2013related orphan receptor \u03b3t (ROR\u03b3t) and displayed a pathogenic Th17 cellular phenotype similar to colonic Th17 cells. Adoptive transfer of ROR\u03b3t-deficient naive CD4+ T cells failed to cause brain inflammation and neurobehavioral disorders in Rag1\u2212\/\u2212 recipients, with significantly less brain infiltration of CD4+ T cells. The finding is mirrored in chronic dextran sulfate sodium\u2013induced colitis in Rorcfl\/fl Cd4-Cre mice that showed lower frequency of brain-infiltrating CD4+ T cells and astrogliosis despite onset of significantly more severe colitis compared with wild-type mice. These findings suggest that pathogenic ROR\u03b3t+CD4+ T cells that aggravate colitis migrate preferentially into the brain, contributing to brain inflammation and neurobehavioral disorders, thereby linking colitis severity to neuroinflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.2100869","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T11:10:17Z","timestamp":1649070617000},"page":"2054-2066","source":"Crossref","is-referenced-by-count":34,"title":["ROR\u03b3t-Expressing Pathogenic CD4+ T Cells Cause Brain Inflammation during Chronic Colitis"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-4900","authenticated-orcid":false,"given":"Michel Edwar","family":"Mickael","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-6929","authenticated-orcid":false,"given":"Suniti","family":"Bhaumik","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayanabha","family":"Chakraborti","sequence":"additional","affiliation":[{"name":"Department of Surgery, Neuroscience, and Neurology, O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-0258","authenticated-orcid":false,"given":"Alan A","family":"Umfress","sequence":"additional","affiliation":[{"name":"Department of Surgery, Neuroscience, and Neurology, O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1861-7530","authenticated-orcid":false,"given":"Thomas","family":"van Groen","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Macaluso","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Totenhagen","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3640-3966","authenticated-orcid":false,"given":"Anna G","family":"Sorace","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Alabama at Birmingham , Birmingham, AL"},{"name":"Department of Biomedical Engineering, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A","family":"Bibb","sequence":"additional","affiliation":[{"name":"Department of Surgery, Neuroscience, and Neurology, O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham , Birmingham, AL"},{"name":"Department of Neurology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2921-8348","authenticated-orcid":false,"given":"David G","family":"Standaert","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4029-8043","authenticated-orcid":false,"given":"Rajatava","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"2025021009025171000_r1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S0140-6736(95)90013-6","article-title":"Focal white-matter lesions in brain of patients with inflammatory bowel disease","volume":"345","author":"Geissler","year":"1995","journal-title":"Lancet"},{"key":"2025021009025171000_r2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3389\/fnhum.2016.00460","article-title":"Structural imaging changes and behavioral correlates in patients with Crohn\u2019s disease in remission","volume":"10","author":"Nair","year":"2016","journal-title":"Front. 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