Division of Rheumatology, Huashan Hospital, Shanghai, China.
Division of Endocrinology, Renhe Hospital, Shanghai, China.
Innate Immun. 2020 May;26(4):294-300. doi: 10.1177/1753425919886643. Epub 2019 Nov 21.
Both NLRP3 inflammasome and Th17 cells play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here we tried to investigate whether leptin promotes the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome. Th17 cells induced from MRL/Mp-Fas lpr mice splenocytes under Th17 polarizing condition were treated with leptin at scalar doses during the last 18 h of culture. The mRNA levels of IL-17A, IL-17F, RORγt, IL-1β, IL-18, NLRP3, ASC, and IL-1R1 were detected by quantitative PCR. IL-17A, IL-17F, IL-1β, and IL-18 were tested by ELISA, while the activity of caspase-1 and number of Th17 cells were counted by flow cytometry before/after inhibition of the NLRP3 inflammasome. We found that leptin pushed up the expression of IL-17A, IL-17F, NLRP3, and IL-1β and increased the number of Th17 cells in lupus mice, while the expression of IL-17A, RORγt, and IL-1β and the number of Th17 cells were decreased after inhibition of the NLRP3 inflammasome. Leptin promoted the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome.
NLRP3 炎性小体和 Th17 细胞在系统性红斑狼疮 (SLE) 的发病机制中都起着重要作用。在这里，我们试图研究瘦素是否通过激活 NLRP3 炎性小体来促进狼疮小鼠 Th17 细胞的分化。在 Th17 极化条件下，从 MRL/Mp-Fas lpr 小鼠脾细胞中诱导 Th17 细胞，在培养的最后 18 小时用瘦素以比例剂量处理。通过定量 PCR 检测 IL-17A、IL-17F、RORγt、IL-1β、IL-18、NLRP3、ASC 和 IL-1R1 的 mRNA 水平。通过 ELISA 检测 IL-17A、IL-17F、IL-1β 和 IL-18，在用 NLRP3 炎性小体抑制剂处理前后通过流式细胞术计数 caspase-1 活性和 Th17 细胞数量。我们发现，瘦素上调了狼疮小鼠中 IL-17A、IL-17F、NLRP3 和 IL-1β 的表达，并增加了 Th17 细胞的数量，而抑制 NLRP3 炎性小体后，IL-17A、RORγt 和 IL-1β 的表达和 Th17 细胞的数量减少。瘦素通过激活 NLRP3 炎性小体促进狼疮小鼠 Th17 细胞的分化。
