Increased expression of IL-1R8 and a possible immunomodulatory role of its ligand IL-37 in allergic rhinitis patients
Increased expression of IL-1R8 and a possible immunomodulatory role of its ligand IL-37 in allergic rhinitis patients
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过敏性鼻炎患者中 IL-1R8 表达增加及其配体 IL-37 可能具有免疫调节作用
DOI：
10.1016/j.intimp.2018.04.002
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发表时间：
2018-07-01
影响因子：
5.6
通讯作者：
Hu, Guo-Hua
中科院分区：
文献类型：
--
作者：
Li, Cong;Shen, Yang;Hu, Guo-Hua
过敏性鼻炎（AR）是一种由T细胞异常反应引起的慢性炎症性气道疾病。辅助性T细胞(Th)-17和Th2细胞是参与AR发病机制的CD4(+) T细胞亚群。据报道，抑制这些Th17和Th2细胞的过度反应是治疗AR患者的有效方法，人们正在不断努力寻找调节这些细胞功能的新方法。最近的研究表明，IL-1R8及其配体IL-37负向调节免疫反应。在本研究中，我们探讨了IL-37/IL-1R8轴在AR患者中的免疫调节作用。我们发现IL-1R8在树突状细胞（dc）和静止CD4(+) T细胞上的表达非常低，但在T细胞激活后CD4(+) T细胞上的表达强烈增加。此外，AR患者CD4(+) T细胞上IL-1R8的表达明显高于健康对照组。IL-1R8配体IL-37可作用于CD4(+) T细胞抑制IL-17和IL-4的产生，但不影响dc诱导的IL-17和IL-4产生的CD4(+) T细胞应答。同时，重组IL-37 （IL-37）不影响dc产生IL-6、IL-113和IL-10，也不影响dc中共刺激分子（包括CD80、CD40、CD86和HLA-DR）的表达。因此，IL-37可能主要通过CD4(+) T细胞调节变应性鼻炎的异常T细胞免疫反应，而不是通过dc。IL-37/IL-1R8轴的免疫调节作用表明该轴在AR中的治疗潜力。
Allergic rhinitis (AR) is a chronic inflammatory airway disease that is caused by an abnormal T cell response. T helper (Th)-17 cells and Th2 cells are the CD4(+) T cell subsets implicated in the pathogenesis of AR. The suppression of excessive responses of these Th17 and Th2 cells has been reported to be an effective therapeutic approach to treat AR patients, and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Recent studies have shown that IL-1R8 and its ligand IL-37 negatively regulate the immune response. In this study, we investigated the immunomodulatory the roles of IL-37/IL-1R8 axis in AR patients. We found that IL-1R8 expression was very low on dendritic cells (DCs) and resting CD4(+) T cells but increased strongly on CD4(+) T cells following T cell activation. Furthermore, IL-1R8 expression on CD4(+) T cells was markedly higher in AR patients than in healthy controls. The IL-1R8 ligand IL-37 could act on CD4(+) T cells to inhibit IL-17 and IL-4 production but could not influence DC-induced IL-17- and IL-4-producing CD4(+) T cell responses. Meanwhile, recombinant IL-37 (rIL-37) did not influence IL-6, IL-113, and IL-10 production by DCs and expression of co-stimulatory molecules (including CD80, CD40, CD86 and HLA-DR) in DCs. Thus, IL-37 may regulate aberrant T cell immune response of allergic rhinitis mainly through CD4(+) T cells, not DCs. The immunomodulatory roles of the IL-37/IL-1R8 axis indicate the therapeutic potential of this axis in AR.