First Author | Tanaka T | Year | 2014 |
Journal | Sci Rep | Volume | 4 |
Pages | 5412 | PubMed ID | 24958459 |
Mgi Jnum | J:279618 | Mgi Id | MGI:6219324 |
Doi | 10.1038/srep05412 | Citation | Tanaka T, et al. (2014) PPARbeta/delta activation of CD300a controls intestinal immunity. Sci Rep 4:5412 |
abstractText | Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARbeta/delta (peroxisome proliferator-activated receptor beta/delta) 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. |