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Sci Rep. 2014 Jun 24;4:5412. doi: 10.1038/srep05412.

PPARβ/δ activation of CD300a controls intestinal immunity.

Author information

1
Laboratory for Systems Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
2
Department of Immunology, Faculty of Medicine, Center for TARA and Japan Science and Technology Agency, CREST, University of Tsukuba, Tsukuba 305-8575, Japan.
3
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.
4
Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
5
Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
6
Gastroenterology Division, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
7
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
8
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.
9
Laboratory for Vascular Biology, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
10
Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
11
Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
12
Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
13
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
14
Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.

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.

PMID:
24958459
PMCID:
PMC4067692
DOI:
10.1038/srep05412
[Indexed for MEDLINE]
Free PMC Article

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