PPARβ/δ activation of CD300a controls intestinal immunity

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

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Cell Line, Tumor
  • Diet, High-Fat / adverse effects
  • HEK293 Cells
  • Humans
  • Inflammation / etiology
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / immunology*
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • PPAR delta / genetics
  • PPAR delta / immunology*
  • PPAR delta / metabolism
  • PPAR-beta / genetics
  • PPAR-beta / immunology*
  • PPAR-beta / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Weight Gain / genetics
  • Weight Gain / immunology

Substances

  • Antigens, CD
  • CD300A protein, human
  • Interleukin-6
  • LMIR1 protein, mouse
  • Lipopolysaccharides
  • PPAR delta
  • PPAR-beta
  • Receptors, Immunologic
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4