Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
UO Nefrologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Front Immunol. 2021 Mar 16;12:639370. doi: 10.3389/fimmu.2021.639370. eCollection 2021.
Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease with variable clinical presentation, typically characterized by a relapsing-remitting course. SLE has a multifactorial pathogenesis including genetic, environmental, and hormonal factors that lead to loss of tolerance against self-antigens and autoantibody production. Mortality in SLE patients remains significantly higher than in the general population, in part because of the limited efficacy of available treatments and the associated toxicities. Therefore, novel targeted therapies are urgently needed to improve the outcomes of affected individuals. Erythropoietin (EPO), a kidney-produced hormone that promotes red blood cell production in response to hypoxia, has lately been shown to also possess non-erythropoietic properties, including immunomodulatory effects. In various models of autoimmune diseases, EPO limits cell apoptosis and favors cell clearance, while reducing proinflammatory cytokines and promoting the induction of regulatory T cells. Notably, EPO has been shown to reduce autoimmune response and decrease disease severity in mouse models of SLE. Herein, we review EPO's non-erythropoietic effects, with a special focus on immune modulating effects in SLE and its potential clinical utility.
系统性红斑狼疮 (SLE) 是一种多器官自身免疫性疾病，具有多变的临床表现，通常以反复发作-缓解为特征。SLE 的发病机制包括遗传、环境和激素等多种因素，这些因素导致机体对自身抗原的耐受性丧失和自身抗体的产生。SLE 患者的死亡率仍然明显高于普通人群，部分原因是现有治疗方法的疗效有限，以及相关的毒性作用。因此，迫切需要新型靶向治疗来改善受影响个体的预后。促红细胞生成素 (EPO) 是一种由肾脏产生的激素，可在缺氧时促进红细胞生成，最近已被证明还具有非红细胞生成性特性，包括免疫调节作用。在各种自身免疫性疾病模型中，EPO 可限制细胞凋亡并促进细胞清除，同时减少促炎细胞因子并促进调节性 T 细胞的诱导。值得注意的是，EPO 已被证明可减少 SLE 小鼠模型中的自身免疫反应并降低疾病严重程度。本文综述了 EPO 的非红细胞生成性作用，特别关注其在 SLE 中的免疫调节作用及其潜在的临床应用。
