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

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98 Citations (Scopus)

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 CD45RBhighCD4+ 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.

Original languageEnglish
Pages (from-to)183-197
Number of pages15
JournalCell Host and Microbe
Volume18
Issue number2
DOIs
Publication statusPublished - 2015 Aug 12

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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    Tang, C., Kamiya, T., Liu, Y., Kadoki, M., Kakuta, S., Oshima, K., Hattori, M., Takeshita, K., Kanai, T., Saijo, S., Ohno, N., & Iwakura, Y. (2015). Inhibition of dectin-1 signaling ameliorates colitis by inducing lactobacillus-mediated regulatory T cell expansion in the intestine. Cell Host and Microbe, 18(2), 183-197. https://doi.org/10.1016/j.chom.2015.07.003