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Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARβ/δ (peroxisome proliferator-activated receptor β/δ) 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.

Citation

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, Takashi Minami, Youichiro Wada, Koutaro Yokote, Takefumi Doi, Takao Hamakubo, Johan Auwerx, Frank J Gonzalez, Atsushi Nakajima, Hiroyuki Aburatani, Makoto Naito, Akira Shibuya, Tatsuhiko Kodama, Juro Sakai. PPARβ/δ activation of CD300a controls intestinal immunity. Scientific reports. 2014;4:5412

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PMID: 24958459

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