title: PPARβ/δ activation of CD300a controls intestinal immunity.
abstract: 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.
authors: Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Toshiya
authors: T
authors: Tanaka
authors: Department of Immunology, Faculty of Medicine, Center for TARA and Japan Science and Technology Agency, CREST, University of Tsukuba, Tsukuba 305-8575, Japan.
authors: Satoko
authors: S
authors: Tahara-Hanaoka
authors: Department of Immunology, Faculty of Medicine, Center for TARA and Japan Science and Technology Agency, CREST, University of Tsukuba, Tsukuba 305-8575, Japan.
authors: Tsukasa
authors: T
authors: Nabekura
authors: Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Kaori
authors: K
authors: Ikeda
authors: 1] Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan [2] Peruseus Proteomics, Tokyo 153-0041, Japan.
authors: Shuying
authors: S
authors: Jiang
authors: Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Shuichi
authors: S
authors: Tsutsumi
authors: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Takeshi
authors: T
authors: Inagaki
authors: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Kenta
authors: K
authors: Magoori
authors: Gastroenterology Division, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors: Takuma
authors: T
authors: Higurashi
authors: Gastroenterology Division, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors: Hirokazu
authors: H
authors: Takahashi
authors: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
authors: Keisuke
authors: K
authors: Tachibana
authors: 1] Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [2] Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors: Yuya
authors: Y
authors: Tsurutani
authors: Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Sana
authors: S
authors: Raza
authors: Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Motonobu
authors: M
authors: Anai
authors: Laboratory for Vascular Biology, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Takashi
authors: T
authors: Minami
authors: Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Youichiro
authors: Y
authors: Wada
authors: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors: Koutaro
authors: K
authors: Yokote
authors: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
authors: Takefumi
authors: T
authors: Doi
authors: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Takao
authors: T
authors: Hamakubo
authors: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors: Johan
authors: J
authors: Auwerx
authors: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors: Frank J
authors: FJ
authors: Gonzalez
authors: Gastroenterology Division, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors: Atsushi
authors: A
authors: Nakajima
authors: Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Hiroyuki
authors: H
authors: Aburatani
authors: Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors: Makoto
authors: M
authors: Naito
authors: Department of Immunology, Faculty of Medicine, Center for TARA and Japan Science and Technology Agency, CREST, University of Tsukuba, Tsukuba 305-8575, Japan.
authors: Akira
authors: A
authors: Shibuya
authors: Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Tatsuhiko
authors: T
authors: Kodama
authors: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors: Juro
authors: J
authors: Sakai
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D059305:Diet, High-Fat / Q000009:adverse effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D047494:PPAR delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D048068:PPAR-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D015430:Weight Gain / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; C515070:CD300A protein, human; D015850:Interleukin-6; C476771:LMIR1 protein, mouse; D008070:Lipopolysaccharides; D047494:PPAR delta; D048068:PPAR-beta; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4