Assistant Professor Albert Einstein College of Medicine Bronx, New York, United States
Disclosure(s):
Maria Cecilia Campos Canesso, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
