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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Cell Line, Tumor
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Diet, High-Fat / adverse effects
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HEK293 Cells
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Humans
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Inflammation / etiology
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Inflammation / genetics
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Inflammation / immunology
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Intestinal Mucosa / metabolism
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Intestines / immunology*
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Lipopolysaccharides / immunology
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Lipopolysaccharides / pharmacology
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Macrophages / immunology
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Macrophages / metabolism
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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PPAR delta / genetics
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PPAR delta / immunology*
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PPAR delta / metabolism
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PPAR-beta / genetics
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PPAR-beta / immunology*
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PPAR-beta / metabolism
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology*
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Receptors, Immunologic / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / immunology
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Toll-Like Receptor 4 / immunology
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Toll-Like Receptor 4 / metabolism
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Transcriptome / genetics
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Transcriptome / immunology
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Weight Gain / genetics
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Weight Gain / immunology
Substances
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Antigens, CD
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CD300A protein, human
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Interleukin-6
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LMIR1 protein, mouse
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Lipopolysaccharides
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PPAR delta
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PPAR-beta
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Receptors, Immunologic
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Tlr4 protein, mouse
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Toll-Like Receptor 4