Dysregulation of γδ intraepithelial lymphocytes precedes Crohn's disease-like ileitis.

ABSTRACT: Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) provide immunosurveillance of the intestinal barrier but are reduced in patients with active Crohn's disease (CD). Here, we report an underappreciated role for γδ IELs in maintaining immunological tolerance during the onset and progression of CD-like ileitis using TNF^ΔARE/+ mice. We found that TNF-induced down-regulation of epithelial hepatocyte nuclear factor 4-gamma/butyrophilin is followed by a loss of ileal Vγ7 IELs and impaired barrier surveillance before the histological onset of disease. A reduction of immunoregulatory CD39⁺ γδ IELs coincided with the influx of immature, peripheral CD39^neg γδ T cells into the epithelium, leading to an expansion of induced IELs, whereas an earlier

SUBMITTER: Xu W 

PROVIDER: S-EPMC12085862 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature