TY - JOUR
T1 - Inhibition of dectin-1 signaling ameliorates colitis by inducing lactobacillus-mediated regulatory T cell expansion in the intestine
AU - Tang, Ce
AU - Kamiya, Tomonori
AU - Liu, Yang
AU - Kadoki, Motohiko
AU - Kakuta, Shigeru
AU - Oshima, Kenshiro
AU - Hattori, Masahira
AU - Takeshita, Kozue
AU - Kanai, Takanori
AU - Saijo, Shinobu
AU - Ohno, Naohito
AU - Iwakura, Yoichiro
N1 - Funding Information:
We thank Sachiko Kubo for her excellent technical assistance. This work was supported by the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry (Y.I.); by CREST (Y.I.); and by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Y.I. and C.T.).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/8/12
Y1 - 2015/8/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2015.07.003
DO - 10.1016/j.chom.2015.07.003
M3 - Article
C2 - 26269954
AN - SCOPUS:84954452665
SN - 1931-3128
VL - 18
SP - 183
EP - 197
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -
