T-cell receptor repertoire alterations drive pathological gut immunological and microbial signatures in humans and mice with hypomorphic RAG deficiency

Mechanistic knowledge about the homeostatic interplay between T cell-mediated immunity and gut microbiota is still limited. We aimed to investigate how restriction of the T-cell receptor (TCR) repertoire (VDJ region) may influence gut microbiota composition, causing tissue inflammation and disruption of peripheral immune tolerance. Based on the clinical observation of colonic inflammation in patients with partial RAG deficiency (pRD), we applied a multi-omics strategy to study a mouse model of hypomorphic Rag1 deficiency (Rag1 mutant mice) with spontaneous development of colitis.