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- Title
PPARβ/δ activation of CD300a controls intestinal immunity.
- Authors
Toshiya Tanaka; Satoko Tahara-Hanaoka; Tsukasa Nabekura; Kaori Ikeda; Shuying Jiang; Shuichi Tsutsumi; Takeshi Inagaki; Kenta Magoori; Takuma Higurashi; Hirokazu Takahashi; Keisuke Tachibana; Yuya Tsurutani; Sana Raza; Motonobu Anai; Minami, Takashi; Youichiro Wada; Koutaro Yokote; Takefumi Doi; Takao Hamakubo; Auwerx, Johan
- Abstract
Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARb/d (peroxisome proliferator- activated receptor b/d) 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 Cd300a2/2 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 Cd300a2/2 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.
- Subjects
HOMEOSTASIS; PEROXISOME proliferator-activated receptors; TYROSINE; HIGH-fat diet; LYMPH nodes; TRIGLYCERIDES; TOLL-like receptors
- Publication
Scientific Reports, 2014, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep05412