A microbiome-reactive TMIGD2(hi) Th17 subset is spatially enriched at the intestinal epithelium and expanded in inflammatory bowel disease.

An epithelial-localized, SusC-reactive Th17 subset expressing TMIGD2 is expanded in inflammatory bowel disease and is BACH2 lo and GZMA hi.

• Why it matters: Limited knowledge of CD4+ T cell specificities and their functional phenotypes blocks mechanistic understanding of mucosal homeostasis and microbiome-driven inflammation in IBD.
• What they did: Using single-cell profiling, the study analyzed SusC-specific and total CD4+ T cell landscapes in intestinal tissues from IBD patients, linking TCR specificities with phenotypes.
• The result: Phenotypic diversification of Th17 cells in IBD was observed, enabling tracking of commensal-specific T cell responses to define specialized Th17 subsets linked to loss of tolerance to the microbiome.