English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Neurobehavioral disorders and brain abnormalities have been extensively reported in both Crohn's 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's 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  -/- 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-related orphan receptor γt (RORγt) and displayed a pathogenic Th17 cellular phenotype similar to colonic Th17 cells. Adoptive transfer of RORγt-deficient naive CD4 + T cells failed to cause brain inflammation and neurobehavioral disorders in Rag1  -/- recipients, with significantly less brain infiltration of CD4 + T cells. The finding is mirrored in chronic dextran sulfate sodium-induced colitis in Rorc fl/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 RORγt + CD4 + T cells that aggravate colitis migrate preferentially into the brain, contributing to brain inflammation and neurobehavioral disorders, thereby linking colitis severity to neuroinflammation.

RORγt-Expressing Pathogenic CD4+ T Cells Cause Brain Inflammation during Chronic Colitis