Mesenteric lymph node CD11b− CD103+ PD‐L1High dendritic cells highly induce regulatory T cells. Issue 1 (1st June 2017) - Shiokawa, Aya
Summary: 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. Abstract : Dendritic cells in mesenteric lymph nodes were classified into four subsets based on CD11b, CD103 and PD‐L1 expression. Among them, the CD11b − CD103 + PD‐L1 High subset highly induced Foxp3 + regulatory T cells. Our results suggest that these cells capture luminal antigens in the intestine, migrate to mesenteric lymph nodes, induce regulatory T cells through transforming growth factor‐β activation, and may be important in oral tolerance induction.