Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5.
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.
Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Satoshi
S
Uematsu
Kosuke
K
Fujimoto
Myoung Ho
MH
Jang
Bo-Gie
BG
Yang
Yun-Jae
YJ
Jung
Mika
M
Nishiyama
Shintaro
S
Sato
Tohru
T
Tsujimura
Masafumi
M
Yamamoto
Yoshifumi
Y
Yokota
Hiroshi
H
Kiyono
Masayuki
M
Miyasaka
Ken J
KJ
Ishii
Shizuo
S
Akira
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005408:Flagellin / Q000276:immunology; D005434:Flow Cytometry; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis*; D014212:Tretinoin / Q000276:immunology / Q000378:metabolism
D007070:Immunoglobulin A; D051198:Toll-Like Receptor 5; D005408:Flagellin; D014212:Tretinoin