引用

炎症的特征是白细胞涌入和激活组织损伤部位。在招募时，免疫细胞被激活，并可分泌促炎细胞因子和化学引诱剂，可调节细胞反应和白细胞运输。然而，如果炎症发生不当，它会导致宿主不必要的组织损伤或影响代谢过程(例如葡萄糖代谢或骨代谢)。有证据表明，肥胖期间脂肪组织也会发生炎症，脂肪组织白细胞分泌细胞因子，可导致全身慢性炎症。调节炎症和调节其对代谢的影响的机制尚不完全清楚。为了帮助澄清是什么因素介导炎症，我们试图确定趋化素受体CMKLR1在介导免疫细胞运输到炎症组织中可能发挥的作用。我们发现CMKLR1在小鼠腹腔巨噬细胞中表达，并能在体外迁移到趋化素中。CMKLR1被TGF?并被促炎细胞因子和TLR配体下调。此外，我们发现CMKLR1加剧了实验小鼠自身免疫性脑脊髓炎(EAE)的进展。 Chemerin was expressed in inflamed central nervous system (CNS) tissue, and microglial cells and CNS-associated myeloid dendritic cells expressed CMKLR1 in mice with EAE. Additionally, we discovered CCRL2 as a novel receptor for chemerin and determined it is a non-signaling decoy receptor which may bind and present chemerin to CMKLR1. We found that CCRL2 is expressed by mouse mast cells and can enhance tissue swelling and tissue leukocyte infiltration during mast cell-dependent passive cutaneous anaphylaxis. In an attempt to uncover a role for chemerin/CMKLR1 in obesity development or obesity-related inflammation, we discovered an unexpected role for the pro-inflammatory cytokine, IL-17, in adipocyte metabolism. IL-17 was upregulated in obese adipose tissue by T cells. IL-17 KO mice were more susceptible to diet-induced obesity. IL-17 inhibited adipocyte development and insulin stimulated glucose uptake by adipocytes. Furthermore, young IL-17 deficient mice were more insulin sensitive than their WT counterparts. Overall, our data indicate a role for chemerin and chemerin receptors in leukocyte migration and function in inflammatory diseases, and suggest that IL-17 regulates metabolic responses associated with obesity.