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

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.

• Authors: Ce Tang, Tomonori Kamiya, Yang Liu, Motohiko Kadoki, Shigeru Kakuta, Kenshiro Oshima, Masahira Hattori, Kozue Takeshita, Takanori Kanai, Shinobu Saijo, Naohito Ohno, Yoichiro Iwakura
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 18 Issue 2 Pg. 183-97 (Aug 12 2015) ISSN: 1934-6069 [Electronic] United States
• PMID: 26269954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Lectins, C-Type
• dectin 1

Topics

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