Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Department of Internal Medicine, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
Hum Immunol. 2023 Apr;84(4):301-310. doi: 10.1016/j.humimm.2023.01.009. Epub 2023 Feb 6.
In addition to malignancies, survivin (a member of the apoptosis inhibitor family) has been implicated in the pathogenesis of inflammatory disorders, including autoimmune and allergic diseases. Survivin is constantly expressed in the proliferating hematopoietic progenitor cells, and it is re-expressed in the mature cells of the innate and adaptive immunity, upon activation. Survivin enhances the expression of co-stimulatory molecules and MHC class II molecules in dendritic cells, and promotes the lifespan of macrophages, neutrophils, and eosinophils, while suppressing natural killer (NK) cell activity. Survivin has been implicated in T cell maturation, T cell expansion, effector CD4 T cell differentiation, maintenance of memory CD4 T and CD8 T cells, as well as antibody production. Upregulated expression of survivin was indicated in the T cells as well as various samples collected from allergic patients. Survivin can contribute to the pathogenesis of allergic diseases via the promotion of the Th2 polarization, promoting IL-4 expression, compromising activation-induced cell death (AICD) in Th2 cells, and preventing apoptosis of eosinophils, as well as, amplification of eosinophilia. Moreover, survivin can interfere with clonal deletion of autoreactive T and B cells, as well as suppress Treg cell development and activity supporting the development of autoimmune diseases. This review discusses the role of survivin in immunity, allergy and autoimmunity as well as provides evidence that survivin may be considered as a novel therapeutic target for the treatment of allergic and autoimmune diseases.
除恶性肿瘤外，凋亡抑制因子家族成员 survivin 也与炎症性疾病的发病机制有关，包括自身免疫和过敏性疾病。Survivin 在增殖的造血祖细胞中持续表达，并在固有和适应性免疫的成熟细胞被激活后重新表达。Survivin 增强树突状细胞共刺激分子和 MHC Ⅱ类分子的表达，并促进巨噬细胞、中性粒细胞和嗜酸性粒细胞的寿命，同时抑制自然杀伤 (NK) 细胞的活性。Survivin 参与 T 细胞成熟、T 细胞扩增、效应性 CD4 T 细胞分化、记忆 CD4 T 和 CD8 T 细胞的维持以及抗体产生。过敏性疾病患者的 T 细胞和各种样本中均显示 survivin 表达上调。Survivin 可通过促进 Th2 极化、促进 IL-4 表达、损害 Th2 细胞的活化诱导细胞死亡 (AICD)、防止嗜酸性粒细胞凋亡以及放大嗜酸性粒细胞增多，从而促进过敏性疾病的发病机制。此外，survivin 可干扰自身反应性 T 和 B 细胞的克隆清除，并抑制 Treg 细胞的发育和活性，从而支持自身免疫性疾病的发展。本文综述了 survivin 在免疫、过敏和自身免疫中的作用，并提供了证据表明 survivin 可能被认为是治疗过敏性和自身免疫性疾病的新的治疗靶点。
