PPARβ/δ activation of CD300a controls intestinal immunity.-猫眼课题宝

DOI：

10.1038/srep05412

发表时间：

2014-06-24

期刊：

Scientific reports

影响因子：

4.6

通讯作者：

中科院分区：

综合性期刊3区

文献类型：

作者：

Tanaka T;Tahara-Hanaoka S;Nabekura T;Ikeda K;Jiang S;Tsutsumi S;Inagaki T;Magoori K;Higurashi T;Takahashi H;Tachibana K;Tsurutani Y;Raza S;Anai M;Minami T;Wada Y;Yokote K;Doi T;Hamakubo T;Auwerx J;Gonzalez FJ;Nakajima A;Aburatani H;Naito M;Shibuya A;Kodama T;Sakai J

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067692/?report=classic

巨噬细胞对维持肠道免疫稳态具有重要作用。在这里，我们发现PPARβ/δ（过氧化物酶体增殖激活受体β/δ）直接调节巨噬细胞中的CD300a，这些巨噬细胞表达含有酪氨酸基抑制基序（ITIM）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。

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.