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Mucosal-associated invariant T cells in Giant Cell Arteritis
Journal of Autoimmunity ( IF 12.8 ) Pub Date : 2021-05-14 , DOI: 10.1016/j.jaut.2021.102652
Thibault Ghesquière 1 , Marion Ciudad 1 , André Ramon 2 , Hélène Greigert 1 , Claire Gerard 3 , Claudie Cladière 1 , Marine Thébault 1 , Coraline Genet 3 , Hervé Devilliers 4 , François Maurier 5 , Paul Ornetti 6 , Valérie Quipourt 7 , Pierre-Henry Gabrielle 8 , Catherine Creuzot-Garcher 8 , Georges Tarris 9 , Laurent Martin 9 , Agnès Soudry-Faure 10 , Philippe Saas 11 , Sylvain Audia 1 , Bernard Bonnotte 1 , Maxime Samson 1
Affiliation  

This study aimed to assess the implication of mucosal-associated invariant T (MAIT) cells in GCA. Blood samples were obtained from 34 GCA patients (before and after 3 months of treatment with glucocorticoids (GC) alone) and compared with 20 controls aged >50 years. MAIT cells, defined by a CD3+CD4TCRγδ-TCRVα7.2+CD161+ phenotype, were analyzed by flow cytometry. After sorting, we assessed the ability of MAIT cells to proliferate and produce cytokines after stimulation with anti CD3/CD28 microbeads or IL-12 and IL-18. MAIT were stained in temporal artery biopsies (TAB) by confocal microscopy.

MAIT cells were found in the arterial wall of positive TABs but was absent in negative TAB. MAIT frequency among total αβ-T cells was similar in the blood of patients and controls (0.52 vs. 0.57%; P = 0.43) and not modified after GC treatment (P = 0.82). Expression of IFN-γ was increased in MAIT cells from GCA patients compared to controls (44.49 vs. 32.9%; P = 0.029), and not modified after 3 months of GC therapy (P = 0.82). When they were stimulated with IL-12 and IL-18, MAIT from GCA patients produced very high levels of IFN-γ and displayed a stronger proliferation compared with MAIT from controls (proliferation index 3.39 vs. 1.4; P = 0.032).

In GCA, the functional characteristics of MAIT cells are modified toward a pro-inflammatory phenotype and a stronger proliferation capability in response to IL-12 and IL-18, suggesting that MAIT might play a role in GCA pathogenesis. Our results support the use of treatments targeting IL-12/IL-18 to inhibit the IFN-γ pathway in GCA.



中文翻译:

巨细胞动脉炎中的黏膜相关不变 T 细胞

本研究旨在评估黏膜相关不变 T (MAIT) 细胞在 GCA 中的意义。血液样本取自 34 名 GCA 患者(单独使用糖皮质激素 (GC) 治疗 3 个月之前和之后),并与 20 名年龄 > 50 岁的对照者进行比较。通过流式细胞术分析由CD3 + CD4 - TCRγδ - TCRVα7.2 + CD161 +表型定义的 MAIT 细胞。分选后,我们评估了 MAIT 细胞在抗 CD3/CD28 微珠或 IL-12 和 IL-18 刺激后增殖和产生细胞因子的能力。MAIT 通过共聚焦显微镜在颞动脉活检 (TAB) 中染色。

MAIT 细胞存在于阳性 TAB 的动脉壁中,但在阴性 TAB 中不存在。患者和对照组血液中总 αβ-T 细胞的 MAIT 频率相似(0.52 对 0.57%;P = 0.43),并且在 GC 治疗后未改变(P = 0.82)。与对照组相比,来自 GCA 患者的 MAIT 细胞中 IFN-γ 的表达增加(44.49 对 32.9%;P = 0.029),并且在 GC 治疗 3 个月后未改变(P = 0.82)。当他们用 IL-12 和 IL-18 刺激时,来自 GCA 患者的 MAIT 产生了非常高水平的 IFN-γ,并且与来自对照组的 MAIT 相比,表现出更强的增殖(增殖指数 3.39 对 1.4;P = 0.032)。

在 GCA 中,MAIT 细胞的功能特征被修饰为促炎表型和响应 IL-12 和 IL-18 的更强增殖能力,表明 MAIT 可能在 GCA 发病机制中发挥作用。我们的结果支持使用靶向 IL-12/IL-18 的治疗来抑制 GCA 中的 IFN-γ 途径。

更新日期:2021-05-14
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