Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Front Immunol. 2023 Mar 10;14:1128270. doi: 10.3389/fimmu.2023.1128270. eCollection 2023.
Several studies implicate Th17-cells and its cytokine (IL-17) in disease pathogenesis of spondyloarthritis (SpA), with available evidence supporting a pathogenic role of CD8+ T-cells. However, data on the involvement of CD8+ mucosal-associated invariant T-cells (MAIT) and their phenotypic characterization and inflammatory function including IL-17 and Granzyme A production in a homogenous population of SpA-patients with primarily axial disease (axSpA) are lacking.
Quantify and characterize the phenotype and function of circulating CD8+MAIT-cells in axSpA-patients with primarily axial disease.
Blood samples were obtained from 41 axSpA-patients and 30 age- and sex-matched healthy controls (HC). Numbers and percentages of MAIT-cells (defined as CD3CD8CD161TCR ) were determined, and production of IL-17 and Granzyme A (GrzA) by MAIT-cells were examined by flow cytometry upon stimulation. Serum IgG specific for CMV was measured by ELISA.
No significant differences in numbers and percentages of circulating MAIT-cells were found between axSpA-patients and HCr zijn meer resultaten de centrale memory CD8 T cellen. cellen van patirculating MAIT cells.. Further phenotypic analysis revealed a significant decrease in numbers of central memory MAIT-cells of axSpA-patients compared to HC. The decrease in central memory MAIT-cells in axSpA patients was not attributed to an alteration in CD8 T-cell numbers, but correlated inversely with serum CMV-IgG titers. Production of IL-17 by MAIT-cells was comparable between axSpA-patients and HC, whereas a significant decrease in the production of GrzA by MAIT-cells from axSpA-patients was observed.
The decrease in cytotoxic capability of circulating MAIT-cells in axSpA-patients might implicate that these cell types migrate to the inflamed tissue and therefore associate with the axial disease pathogenesis.
多项研究表明 Th17 细胞及其细胞因子(IL-17)在脊柱关节炎(SpA)的发病机制中起作用,现有证据支持 CD8+T 细胞的致病作用。然而,关于 CD8+黏膜相关不变 T 细胞(MAIT)及其表型特征以及包括 IL-17 和 Granzyme A 产生在内的炎症功能在主要为轴性疾病(axSpA)的 SpA 患者同质人群中的参与情况的数据尚缺乏。
定量和描述主要为轴性疾病的 axSpA 患者循环 CD8+MAIT 细胞的表型和功能。
从 41 例 axSpA 患者和 30 名年龄和性别匹配的健康对照者(HC)中采集血样。通过流式细胞术确定 MAIT 细胞(定义为 CD3+CD8+CD161+TCRγδ+)的数量和百分比,并在刺激后检查 MAIT 细胞产生 IL-17 和 Granzyme A(GrzA)的情况。通过 ELISA 测量血清 CMV 特异性 IgG。
axSpA 患者和 HCr 之间循环 MAIT 细胞的数量和百分比无显著差异。细胞的 patirculating MAIT cells.. 进一步的表型分析显示,与 HC 相比,axSpA 患者的中央记忆 MAIT 细胞数量显著减少。axSpA 患者中中央记忆 MAIT 细胞的减少与 CD8 T 细胞数量的改变无关,而是与血清 CMV-IgG 滴度呈负相关。axSpA 患者 MAIT 细胞产生 IL-17 的能力与 HC 相当,而 axSpA 患者 MAIT 细胞产生 GrzA 的能力显著降低。
axSpA 患者循环 MAIT 细胞的细胞毒性能力下降可能意味着这些细胞类型迁移到炎症组织中,因此与轴性疾病的发病机制有关。