Sun Yonglian, Caplazi Patrick, Zhang Juan, Mazloom Anita, Kummerfeld Sarah, Quinones Gabriel, Senger Kate, Lesch Justin, Peng Ivan, Sebrell Andrew, Luk Wilman, Lu Yanmei, Lin Zhonghua, Barck Kai, Young Judy, Del Rio Mariela, Lehar Sophie, Asghari Vida, Lin WeiYu, Mariathasan Sanjeev, DeVoss Jason, Misaghi Shahram, Balazs Mercedesz, Sai Tao, Haley Benjamin, Hass Philip E, Xu Min, Ouyang Wenjun, Martin Flavius, Lee Wyne P, Zarrin Ali A
Department of Immunology, Genentech, South San Francisco, CA 94080;
Department of Pathology, Genentech, South San Francisco, CA 94080;
J Immunol. 2014 Jul 15;193(2):860-70. doi: 10.4049/jimmunol.1400045. Epub 2014 Jun 16.
Paired Ig-like type 2 receptor (PILR)α inhibitory receptor and its counterpart PILRβ activating receptor are coexpressed on myeloid cells. In this article, we report that PILRα, but not PILRβ, is elevated in human rheumatoid arthritis synovial tissue and correlates with inflammatory cell infiltration. Pilrα(-/-) mice produce more pathogenic cytokines during inflammation and are prone to enhanced autoimmune arthritis. Correspondingly, engaging PILRα with anti-PILRα mAb ameliorates inflammation in mouse arthritis models and suppresses the production of proinflammatory cytokines. Our studies suggest that PILRα mediates an important inhibitory pathway that can dampen inflammatory responses.
配对免疫球蛋白样2型受体(PILR)α抑制性受体及其对应的PILRβ激活性受体在髓样细胞上共表达。在本文中,我们报道,人类风湿性关节炎滑膜组织中PILRα升高,而PILRβ未升高,且PILRα与炎性细胞浸润相关。Pilrα(-/-)小鼠在炎症期间产生更多致病性细胞因子,且易于患加重的自身免疫性关节炎。相应地,用抗PILRα单克隆抗体作用于PILRα可改善小鼠关节炎模型中的炎症,并抑制促炎细胞因子的产生。我们的研究表明,PILRα介导一条可抑制炎症反应的重要抑制性途径。