Classical dendritic cells are required for dietary antigen-mediated induction of peripheral Treg cells and tolerance

Abstract

Oral tolerance prevents pathological inflammatory responses to innocuous foreign antigens by peripheral regulatory T cells (pT_reg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure for the 'instruction' of naive CD4⁺ T cells to differentiate into pT_reg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs were dispensable, while classical dendritic cells (cDCs) were critical, for pT_reg cell induction and oral tolerance. CD11b^- cDCs from the gut-draining lymph nodes efficiently induced pT_reg cells and, conversely, loss of transcription factor IRF8-dependent CD11b^- cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in the induction of pT_reg cells and their redundancy during the development of oral tolerance.