Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Exp Biol Med (Maywood). 2021 Jan;246(1):57-65. doi: 10.1177/1535370220956943. Epub 2020 Sep 9.
The participation of interleukin (IL)-17A in diabetic pathogenesis is suggested in animal models of autoimmune diabetes and in patients with type 1 diabetes (T1D), but with some contradictory results. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells is lacking. We showed that IL-17A deficiency alleviated diabetic signs including hyperglycemia, hypoinsulinemia, and inflammatory response in (Akita) mice, a T1D model with spontaneous mutation in gene leading to β-cell apoptosis. IL-17A enhanced inflammatory reaction, oxidative stress, and cell apoptosis but attenuated insulin level in mouse insulin-producing MIN6 cells. IL-17A had also a synergistic destruction to MIN6 cells with streptozotocin (STZ), a pancreatic β-cell-specific cytotoxin. Blocking IL-17 receptor A (IL-17RA) reduced all these deleterious effects of IL-17A on MIN6 cells. The results demonstrate the role and the importance of IL-17A in T1D pathogenesis and suggest a potential therapeutic strategy for T1D targeting IL-17A and/or IL-17RA.
白细胞介素 (IL)-17A 参与自身免疫性糖尿病动物模型和 1 型糖尿病 (T1D) 患者的糖尿病发病机制，但结果存在一些矛盾。特别是，缺乏 IL-17A 对胰腺 β 细胞的直接损伤证据。我们表明，IL-17A 缺乏减轻了自发性基因突变导致 β 细胞凋亡的 T1D 模型 (Akita) 小鼠的糖尿病症状，包括高血糖、低胰岛素血症和炎症反应。IL-17A 增强了炎症反应、氧化应激和细胞凋亡，但降低了小鼠胰岛素分泌 MIN6 细胞中的胰岛素水平。IL-17A 与链脲佐菌素 (STZ)（一种胰腺 β 细胞特异性细胞毒素）也具有协同破坏 MIN6 细胞的作用。阻断 IL-17 受体 A (IL-17RA) 可降低 IL-17A 对 MIN6 细胞的所有这些有害影响。结果表明 IL-17A 在 T1D 发病机制中的作用和重要性，并为针对 IL-17A 和/或 IL-17RA 的 T1D 治疗策略提供了依据。
