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Nature Immunology 9, 769–776 (1 July 2008) | doi:10.1038/ni.1622

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

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

The intestinal cell types responsible for defense against pathogenic organisms remain incompletely characterized. Here we identify a subset of CD11chiCD11bhi 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.