PPARbata/delta activation of CD300a controls intestinal immunity

2013 Fiscal Year Final Research Report

• Project/Area Number: 24650442
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• 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
• 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.

Research Products

• [Journal Article] PPAR beta/delta activation of CD300a controls intestinal immunity (2014)
  • 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
  • Journal Title: Scientific Reports Volume: (in press)
• [Presentation] The immuno-inhibitory receptor CD300A controls intestinal immunity and prevents onset of diabetes through a PPARδdependent pathway (2012)
  • Author(s): Juro Sakai
  • Organizer: 第44回日本動脈硬化学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-07-19
• [Presentation] Epigenomic regulation of inflammation, energy metabolism, and adipogenesis (2012)
  • Author(s): Juro Sakai
  • Organizer: The 2012 Deuel Conference on Lipids
  • Place of Presentation: Palm Springs, California
  • Year and Date: 2012-03-08
• [Remarks]
  • URL: http://www.mm.rcast.u-tokyo.ac.jp/