PPARbata/delta activation of CD300a controls intestinal immunity

我们发现ppar β / δ（过氧化物酶体增殖体激活受体β / δ）直接调节巨噬细胞中的CD300a，巨噬细胞表达含有酪氨酸基抑制基序（ITIM）受体的免疫受体。在缺乏CD300a的小鼠中，高脂肪饮食（HFD）引起慢性肠道炎症，肠道淋巴毛细血管数量减少，肠系膜淋巴结急剧扩大。结果，这些小鼠表现出甘油三酯吸收不良，体重增加减少。Cd300a-/-小鼠腹腔巨噬细胞呈典型的M1活化。脂多糖（LPS）激活toll样受体4 (TLR4)/MyD88信号导致Cd300a-/-巨噬细胞IL-6分泌延长。骨髓移植证实该表型源于白细胞中CD300a的缺乏。这些结果表明cd300a介导的巨噬细胞抑制信号是肠道免疫稳态的关键调节因子。

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.