Banas Magdalena, Zegar Aneta, Kwitniewski Mateusz, Zabieglo Katarzyna, Marczynska Joanna, Kapinska-Mrowiecka Monika, LaJevic Melissa, Zabel Brian A, Cichy Joanna
Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
Department of Dermatology, Zeromski Hospital, Kraków, Poland.
PLoS One. 2015 Feb 6;10(2):e0117830. doi: 10.1371/journal.pone.0117830. eCollection 2015.
Chemerin is a protein ligand for the G protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1. Chemerin is a leukocyte attractant, adipokine, and antimicrobial protein. Although chemerin was initially identified as a highly expressed gene in healthy skin keratinocytes that was downregulated during psoriasis, the regulation of chemerin and its receptors in the skin by specific cytokines and microbial factors remains unexplored. Here we show that chemerin, CMKLR1, CCRL2 and GPR1 are expressed in human and mouse epidermis, suggesting that this tissue may be both a source and target for chemerin mediated effects. In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β. Moreover, we show that human keratinocytes in vitro and mouse skin in vivo respond to specific microbial signals to regulate expression levels of chemerin and its receptors. Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo. Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.
趋化素是G蛋白偶联受体CMKLR1的一种蛋白质配体，也能与两种非典型七螺旋受体CCRL2和GPR1结合。趋化素是一种白细胞吸引剂、脂肪因子和抗菌蛋白。尽管趋化素最初被鉴定为在健康皮肤角质形成细胞中高表达的基因，在银屑病期间会下调，但特定细胞因子和微生物因子对趋化素及其受体在皮肤中的调节作用仍未得到探索。在此我们表明，趋化素、CMKLR1、CCRL2和GPR1在人和小鼠表皮中表达，这表明该组织可能既是趋化素介导作用的来源又是靶点。在人皮肤培养物中，趋化素被银屑病相关的关键细胞因子IL-17和IL-22显著下调，而被急性期细胞因子制瘤素M和IL-1β上调。此外，我们表明体外培养的人角质形成细胞和体内的小鼠皮肤对特定微生物信号作出反应，以调节趋化素及其受体的表达水平。此外，在皮肤感染模型中，趋化素是体内最大杀菌作用所必需的。总之，我们的研究结果揭示了皮肤中趋化素表达以前未被表征的调节因子，并确定了趋化素在皮肤屏障抵御微生物病原体中的生理作用。
