Antigen-presenting cell—T cell interactions shaping immune responses to intestinal antigens 2308241

Abstract Introduction The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens and inducing the differentiation of CD4+ T cells into regulatory (pTreg) or inflammatory (Th) subsets. Methods We combined multiple LIPSTIC tools with interaction-based transcriptomics, mouse genetic approaches, and genetically engineered bacteria to identify APCs that present dietary and microbiota antigens under tolerogenic and inflammatory conditions. Results We show that antigen presentation by distinct subsets of APCs drives specific Th or pTreg differentiation. Microbial or dietary antigen presentation by migratory cDC1s and Rorgt+ APCs was associated with pTreg differentiation. Antigen presentation by intestinal cDC2 subsets results in diverse outcomes, ranging from Th2 or Th17 differentiation to impaired pTreg induction. Conclusion Our data uncover the cellular mechanisms by which T cell differentiation to microbial or dietary antigens is induced based on APCs dynamics. Funding Source K99/R00 Pathway to Independence Award NIAID, NIH Topic Categories Mucosal and Regional Immunology (MUC)