Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR S 959, Immunology-Immunopathology- Immunotherapy (I3), F-75005, Paris, France.
Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Pitié-Salpêtrière, AP-HP, F-75651, Paris, France.
Sci Rep. 2020 Apr 14;10(1):6405. doi: 10.1038/s41598-020-63042-3.
The mechanisms regulating inflammation in large vessels vasculitis (LVV) are poorly understood. Interleukin 33 (IL-33) has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production. We aimed to examine the role of IL-33 in the immunomodulation of T cell activation in LVV. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis (GCA) and 50 healthy donors (HD), using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. We found increased level of IL-33 and its receptor ST2/IL-1R4 in the serum of patient with LVV. Endothelial cells were the main source of IL-33, whereas Th2 cells, Tregs and mast cells (MC) express ST2 in LVV vessels. IL-33 had a direct immunomodulatory impact by increasing Th2 and Tregs. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs (p = 0.008). Stimulation of MC by IL-33 increased indoleamine 2 3-dioxygenase (IDO) activity and IL-2 secretion. IL-33 mRNA expression was significantly correlated with the expression of IL-10 and TGF-β within aorta inflammatory lesions. To conclude, our findings suggest that IL-33 may exert a critical immunoregulatory role in promoting Tregs and Th2 cells in LVV.
调控大动脉炎（LVV）炎症的机制尚未完全阐明。白细胞介素 33（IL-33）已被证明可通过增强 Th2 细胞因子的产生来许可先天和适应性免疫。我们旨在研究 IL-33 在 LVV 中调节 T 细胞激活的免疫调节作用。通过 Luminex assay、流式细胞术、定量 RT-PCR 和在炎症性主动脉病变中进行免疫荧光分析，测定了 52 例巨细胞动脉炎（GCA）患者和 50 名健康供体（HD）外周血中的 T 细胞稳态和细胞因子产生。我们发现 LVV 患者血清中 IL-33 及其受体 ST2/IL-1R4 水平升高。内皮细胞是 IL-33 的主要来源，而 Th2 细胞、Tregs 和肥大细胞（MC）在 LVV 血管中表达 ST2。IL-33 通过增加 Th2 和 Tregs 具有直接的免疫调节作用。IL-33 和 MC 通过诱导 Tregs 比例增加 6.1 倍（p = 0.008）进一步增强 Th2 和调节反应。IL-33 刺激 MC 可增加吲哚胺 2,3-双加氧酶（IDO）活性和 IL-2 分泌。IL-33 mRNA 表达与主动脉炎症病变中 IL-10 和 TGF-β 的表达显著相关。总之，我们的研究结果表明，IL-33 可能在促进 LVV 中的 Tregs 和 Th2 细胞方面发挥关键的免疫调节作用。
