PPAR?/? activation of CD300a controls intestinal immunity.

ABSTRACT: Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPAR?/? (peroxisome proliferator-activated receptor ?/?) 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.

SUBMITTER: Tanaka T 

PROVIDER: S-EPMC4067692 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature