Inhibition of Dectin-1 Signaling Ameliorates Colitis by Inducing Lactobacillus-Mediated Regulatory T Cell Expansion in the Intestine

Ce Tang; Tomonori Kamiya; Yang Liu; Motohiko Kadoki; Shigeru Kakuta; Kenshiro Oshima; Masahira Hattori; Kozue Takeshita; Takanori Kanai; Shinobu Saijo; Naohito Ohno; Yoichiro Iwakura

doi:10.1016/j.chom.2015.07.003

Inhibition of Dectin-1 Signaling Ameliorates Colitis by Inducing Lactobacillus-Mediated Regulatory T Cell Expansion in the Intestine

Cell Host Microbe. 2015 Aug 12;18(2):183-97. doi: 10.1016/j.chom.2015.07.003.

Authors

Ce Tang¹, Tomonori Kamiya², Yang Liu³, Motohiko Kadoki⁴, Shigeru Kakuta⁵, Kenshiro Oshima⁶, Masahira Hattori⁶, Kozue Takeshita⁷, Takanori Kanai⁷, Shinobu Saijo⁸, Naohito Ohno⁹, Yoichiro Iwakura¹⁰

Affiliations

¹ 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.
² Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8654, Japan.
³ 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.
⁴ 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.
⁵ 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.
⁶ Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
⁷ Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-5882, Japan.
⁸ 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.
⁹ School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.
¹⁰ 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.

PMID: 26269954
DOI: 10.1016/j.chom.2015.07.003

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colitis / pathology*
Colon / immunology*
Colon / pathology*
Lactobacillus / immunology*
Lectins, C-Type / antagonists & inhibitors*
Lectins, C-Type / genetics
Mice
Mice, Knockout
Signal Transduction*
T-Lymphocytes, Regulatory / immunology*

Substances

Lectins, C-Type
dectin 1