Inhibition of Dectin-1 Signaling Ameliorates Colitis by Inducing Lactobacillus-Mediated Regulatory T Cell Expansion in the Intestine.
Dectin-1, the receptor for β-glucans, protects the host against fungal infection; however, its role in intestinal immunity is incompletely understood. We found that Dectin-1-deficient (Clec7a(-/-)) mice were refractory to both dextran sodium sulfate (DSS)- and CD45RB(high)CD4(+) T cell-induced colitis, and that this resistance was associated with an increase in regulatory T (Treg) cells. The proportion of lactobacilli, especially Lactobacillus murinus, in the commensal microflora was increased in Clec7a(-/-) mouse colons, and accompanied by a decrease in antimicrobial peptides induced by Dectin-1 signaling. L. murinus colonization increased Treg cells in the colon. Oral administration of laminarin, a Dectin-1 antagonist, suppressed the development of DSS-colitis, associated with an increase of L. murinus and Treg cells. Human patients with inflammatory bowel disease were found to have a decreased proportion of closely related Lactobacillus species. These observations suggest that Dectin-1 regulates the homeostasis of intestinal immunity by controlling Treg cell differentiation through modification of microbiota.
Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
Ce
C
Tang
Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8654, Japan.
Tomonori
T
Kamiya
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Renji Hospital Clinical Stem Cell Research Center, Shanghai Jiao Tong University School of Medicine, Shang Hai, 200127, P.R. China.
Yang
Y
Liu
Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Motohiko
M
Kadoki
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Shigeru
S
Kakuta
Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
Kenshiro
K
Oshima
Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
Masahira
M
Hattori
Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-5882, Japan.
Kozue
K
Takeshita
Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-5882, Japan.
Takanori
T
Kanai
Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
Shinobu
S
Saijo
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.
Naohito
N
Ohno
Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama 332-0012, Japan; Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8654, Japan; Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan; Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan. Electronic address: iwakura@rs.tus.ac.jp.
Yoichiro
Y
Iwakura
D000818:Animals; D003092:Colitis / Q000473:pathology*; D003106:Colon / Q000276:immunology* / Q000473:pathology*; D007778:Lactobacillus / Q000276:immunology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000099181:Dectin-1
D037181:Lectins, C-Type; D000099181:Dectin-1