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-L1^High , CD11b^- CD103⁺ PD-L1^High , CD11b^- CD103⁺ PD-L1^Low and CD11b⁺ CD103^- PD-L1^Int . Among them, the CD11b^- CD103⁺ PD-L1^High 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-L1^High 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-L1^High DC subset probably takes up luminal antigens in the intestine, migrates to MLNs, and highly induces regulatory T cells through TGF-β activation.

Keywords: dendritic cells; intestinal immunity; mesenteric lymph nodes; oral tolerance; regulatory T cells.