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

Research output: Contribution to journalArticle

77 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
Externally publishedYes

Fingerprint

Lactobacillus
Regulatory T-Lymphocytes
Colitis
Intestines
Dextran Sulfate
Immunity
Colon
Glucans
Mycoses
Microbiota
Inflammatory Bowel Diseases
Oral Administration
Cell Differentiation
Homeostasis
dectin 1
T-Lymphocytes
Peptides

ASJC Scopus subject areas

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

Cite this

Inhibition of dectin-1 signaling ameliorates colitis by inducing lactobacillus-mediated regulatory T cell expansion in the intestine. / Tang, Ce; Kamiya, Tomonori; Liu, Yang; Kadoki, Motohiko; Kakuta, Shigeru; Oshima, Kenshiro; Hattori, Masahira; Takeshita, Kozue; Kanai, Takanori; Saijo, Shinobu; Ohno, Naohito; Iwakura, Yoichiro.

In: Cell Host and Microbe, Vol. 18, No. 2, 12.08.2015, p. 183-197.

Research output: Contribution to journalArticle

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, vol. 18, no. 2, pp. 183-197. https://doi.org/10.1016/j.chom.2015.07.003
Tang, Ce ; Kamiya, Tomonori ; Liu, Yang ; Kadoki, Motohiko ; Kakuta, Shigeru ; Oshima, Kenshiro ; Hattori, Masahira ; Takeshita, Kozue ; Kanai, Takanori ; Saijo, Shinobu ; Ohno, Naohito ; Iwakura, Yoichiro. / Inhibition of dectin-1 signaling ameliorates colitis by inducing lactobacillus-mediated regulatory T cell expansion in the intestine. In: Cell Host and Microbe. 2015 ; Vol. 18, No. 2. pp. 183-197.
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