Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling.

ABSTRACT: Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) provide continuous surveillance of the intestinal epithelium. We report that mice harboring a microbiota-specific hyperproliferative γδ IEL (γδ^HYP) phenotype also upregulate the expression of the ectonucleotidase CD39, a marker of regulatory γδ T cells. Enhanced TCR and IL-15 signaling correlates with a progression from a naïve-like CD39^neg γδ IEL to a more mature, tissue-adapted CD39^hi IEL population. We found that TCRγδ activation drives CD122-mediated CD39 upregulation on γδ^HYP IELs and increased mucosal IL-15 further amplifies CD39 expression in these cells. Further investigation revealed that CD39 induction requires sustained exposure to the γδ^HYP-associated mi

SUBMITTER: Alonso S 

PROVIDER: S-EPMC12363992 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature