Mesenteric lymph node CD11b− CD103+ PD-L1High dendritic cells highly induce regulatory T cells

Abstract

Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3+ regulatory T cells to regulate immune responses to beneficial or non-harmful agents in the intestine, such as commensal bacteria and foods. Several studies in MLN DCs have revealed that the CD103+ DC subset highly induces regulatory T cells, and another study has reported that MLN DCs from programmed death ligand 1 (PD-L1) -deficient mice could not induce regulatory T cells. Hence, the present study investigated the expression of these molecules on MLN CD11c+ cells. Four distinct subsets expressing CD103 and/or PD-L1 were identified, namely CD11b+ CD103+ PD-L1High, CD11b− CD103+ PD-L1High, CD11b− CD103+ PD-L1Low and CD11b+ CD103− PD-L1Int. Among them, the CD11b− CD103+ PD-L1High DC subset highly induced Foxp3+ T cells. This subset expressed Aldh1a2 and Itgb8 genes, which are involved in retinoic acid metabolism and transforming growth factor-β (TGF-β) activation, respectively. Exogenous TGF-β supplementation equalized the level of Foxp3+ T-cell induction by the four subsets whereas retinoic acid did not, which suggests that high ability to activate TGF-β is determinant for the high Foxp3+ T-cell induction by CD11b− CD103+ PD-L1High DC subset. Finally, this subset exhibited a migratory DC phenotype and could take up and present orally administered antigens. Collectively, the MLN CD11b− CD103+ PD-L1High DC subset probably takes up luminal antigens in the intestine, migrates to MLNs, and highly induces regulatory T cells through TGF-β activation.