Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5

表达 Toll 样受体 5 的固有层树突状细胞对体液和细胞肠道免疫的调节

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作者:Satoshi Uematsu, Kosuke Fujimoto, Myoung Ho Jang, Bo-Gie Yang, Yun-Jae Jung, Mika Nishiyama, Shintaro Sato, Tohru Tsujimura, Masafumi Yamamoto, Yoshifumi Yokota, Hiroshi Kiyono, Masayuki Miyasaka, Ken J Ishii, Shizuo Akira

Abstract

The intestinal cell types responsible for defense against pathogenic organisms remain incompletely characterized. Here we identify a subset of CD11c(hi)CD11b(hi) lamina propria dendritic cells (LPDCs) that expressed Toll-like receptor 5 (TLR5) in the small intestine. When stimulated by the TLR5 ligand flagellin, TLR5(+) LPDCs induced the differentiation of naive B cells into immunoglobulin A-producing plasma cells by a mechanism independent of gut-associated lymphoid tissue. In addition, by a mechanism dependent on TLR5 stimulation, these LPDCs promoted the differentiation of antigen-specific interleukin 17-producing T helper cells and type 1 T helper cells. Unlike spleen DCs, the LPDCs specifically produced retinoic acid, which, in a dose-dependent way, supported the generation and retention of immunoglobulin A-producing cells in the lamina propria and positively regulated the differentiation interleukin 17-producing T helper cells. Our findings demonstrate unique properties of LPDCs and the importance of TLR5 for adaptive immunity in the intestine.

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