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Mesenteric lymph node CD11b − CD103 + PD‐L1 High dendritic cells highly induce regulatory T cells
Author(s) -
Shiokawa Aya,
Kotaki Ryutaro,
Takano Tomohiro,
NakajimaAdachi Haruyo,
Hachimura Satoshi
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12747
Subject(s) - foxp3 , cd11c , immune system , integrin alpha m , microbiology and biotechnology , biology , t cell , antigen , mesenteric lymph nodes , chemistry , antigen presenting cell , cancer research , immunology , phenotype , biochemistry , gene
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.