Identification of human DP8α regulatory T cell sub-populations reactive to health-associated anti-inflammatory gut commensals

While the role of gut microbiota in health has been demonstrated, deciphering the involvement of individual bacterial species in diseases with unmet clinical needs represents a major research interest. Over the last decade, DP8α regulatory T cells (Tregs) have been identified to respond to Faecalibacterium duncaniae and protect against inflammatory bowel diseases (IBD) and acute graft-versus-host disease (aGvHD). To better understand, on the one hand, physiological DP8α Treg activation processes, and, on the other hand, the underlying mechanisms used by anti-inflammatory bacterial species to protect the host, we investigated whether additional key species could be recognized by DP8α Tregs. Here we showed that Blautia obeum, Roseburia intestinalis, and Akkermansia muciniphila indeed represent sources of antigens for DP8α Treg activation and priming, likely through their unique ability to induce tolerogenic antigen presenting cells. This study provides considerable mechanistic insight into the gut microbiota/regulatory T cell interplay and further establishes the role of DP8α Tregs, and their emerging dedicated ability to respond to gut microbiota, in local and systemic homeostasis.