PPARbata/delta activation of CD300a controls intestinal immunity
Project/Area Number |
24650442
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Single-year Grants |
Research Field |
Applied health science
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Research Institution | The University of Tokyo |
Principal Investigator |
SAKAI Juro 東京大学, 先端科学技術研究センター, 教授 (80323020)
|
Co-Investigator(Renkei-kenkyūsha) |
TANAKA Toshiya 東京大学, 先端科学技術研究センター, 特任准教授 (20396930)
|
Project Period (FY) |
2012-04-01 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 生活習慣病 / 腸管免疫 / 核内受容体 / TLR |
Research Abstract |
we show that PPARbeta/delta (peroxisome proliferator-activated receptor beta/delta) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a-/- mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a-/- macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] PPAR beta/delta activation of CD300a controls intestinal immunity2014
Author(s)
Tanaka T, Tahara-Hanaoka S, Nabekura T, Ikeda K, Jiang S, Tsutsumi S, Inagaki T, Magoori K, Higurashi T, Takahashi H, Tachibana K, Tsurutani Y, Raza S, Anai M, Minami T, Wada Y, Yokote K, Doi T, Hamakubo T, Johan A, J. GF, Nakajima A, Aburatani H, Naito M, Shibuya A, Kodama T, Sakai J
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Journal Title
Scientific Reports
Volume: (in press)
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[Journal Article] Direct evidence of chromatin structure change in KLF4 gene caused by pitavastatin in endothelial cells2014
Author(s)
Maejima T, Tanaka; T, Minami; T, Hamakubo; T, Ihara; S, Sakai; J, Nozaki; N, Aburatani; H, Ruan; X, Tanabe; H, Ruan; Y, Endo; A, Kodama; T, Wada Y
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Journal Title
PLOS One IMPRESSED
Volume: impressed
Related Report
Peer Reviewed
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[Journal Article] Sterol-regulatory-element-binding protein 2 and nuclear factor Y control human farnesyl diphosphate synthase expression and affect cell proliferation in hepatoblastoma cells2013
Author(s)
Ishimoto K, Tachibana K, Hanano I, Yamasaki D, Nakamura H, Kawai M, Urano Y, Tanaka T, Hamakubo T, Sakai J, Kodama T, Doi T
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Journal Title
Biochem J
Volume: 429
Issue: 2
Pages: 347-357
DOI
Related Report
Peer Reviewed
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[Journal Article] Human mannose-binding lectin 2 is directly regulated by peroxisome proliferator-activated receptors (PPARs) via a peroxisome proliferator responsive element2013
Author(s)
Tachibana K, Takeuchi K, Inada H, Sugimoto K, Ishimoto K, Yamashita M, Maegawa T, Yamasaki D, Osada S, Tanaka T, Rakug H, Hamakubo T, Sakai J, Kodama T, Doi T
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Journal Title
The Journal of Biochemistry
Volume: 154 (3)
Issue: 3
Pages: 265-73
DOI
Related Report
Peer Reviewed
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[Journal Article] Novel repressor regulates insulin sensitivity through interaction with Foxo12012
Author(s)
Nakae J, Cao Y, Hakuno F, Takemori H, Kawano Y, Sekioka R, Abe T, Kiyonari H, Tanaka T, Sakai J, Takahashi SI, Itoh H
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Journal Title
EMBO J.
Volume: 31
Issue: 10
Pages: 2275-2295
DOI
Related Report
Peer Reviewed
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