Immune micro-niches shape intestinal Treg function

Please note this is an Ad-Hoc seminar. This is a hybrid event - with the speaker attending in-person and viewable on Teams.

The intestinal immune system is adapted to maintain homeostasis to commensal microbiota, whilst poised to defend against invading pathogens. Recognising how the diverse network of immune cells promote tolerance is critical to understanding how to re-establish homeostasis once disrupted by inflammation. T regulatory cells (Treg) are key players in maintaining barrier tolerance, however little is known about the cellular networks and spatial compartments that support tissue Treg phenotype and function in response to microbial antigen. We track the natural history of T cells reactive to the pathobiont Helicobacter hepaticus (Hh) through space and time using in vivo live imaging, photoactivation-guided single cell RNA sequencing (NICHE-seq) and spatial transcriptomics. By following Hhspecific Tregs as they acquire and maintain regulatory function in the anatomical microniches, we identify and validate several pathways that may be enhanced or disrupted to restrain inflammation. Our findings reveal a spatially-driven mechanism of effector Treg function, and demonstrate how knowledge of niche-specific immune interactions could guide more effective tolerance-inducing therapies.