Elevated interleukin (IL)-21 is a common finding in the tissues and/or sera of patients with autoimmune disease. CD4 T cells are the primary producers of IL-21; often the IL-21 producing CD4 T cells will express molecules associated with follicular helper cells (T_FH). Recent work has shown that the CD4 T cell-derived IL-21 is able to promote effector functions and memory differentiation of CD8 T cells in chronic infections and cancer. Autoimmunity has similarities to chronic infections and cancer. However, CD4 T cell-derived IL-21:IL21R signaling in CD8 T cells has not been fully appreciated in the context of autoimmunity. In this review, we assess the current knowledge regarding CD4 T cell-derived IL-21 and IL21R signaling within CD8 T cells and evaluate what implications it has within several autoimmune diseases including systemic lupus erythematous, rheumatoid arthritis, juvenile idiopathic arthritis, type 1 diabetes mellitus, psoriasis, Sjögren's syndrome, vitiligo, antiphospholipid syndrome, pemphigus, and giant cell arteritis.

白细胞介素 (IL)-21 升高是自身免疫性疾病患者组织和/或血清中的常见发现。CD4 T 细胞是 IL-21 的主要生产者；通常，产生 IL-21 的 CD4 T 细胞会表达与滤泡辅助细胞相关的分子（T _FH）。最近的研究表明，CD4 T 细胞衍生的 IL-21 能够促进 CD8 T 细胞在慢性感染和癌症中的效应功能和记忆分化。自身免疫与慢性感染和癌症有相似之处。然而，在自身免疫的背景下，CD8 T 细胞中 CD4 T 细胞衍生的 IL-21:IL21R 信号传导尚未得到充分认识。在这篇综述中，我们评估了关于 CD8 T 细胞内 CD4 T 细胞衍生的 IL-21 和 IL21R 信号传导的当前知识，并评估了它对几种自身免疫性疾病的影响，包括系统性红斑狼疮、类风湿性关节炎、幼年特发性关节炎、1 型糖尿病糖尿病、牛皮癣、干燥综合征、白癜风、抗磷脂综合征、天疱疮和巨细胞动脉炎。