Paris Descartes University, Cochin Institute, CNRS UMR8104, INSERM U1016, Paris, France.
Center of Research on Inflammation INSERM U1149, CNRS ERL8252, Paris Diderot University, Paris, France.
J Autoimmun. 2019 May;99:73-80. doi: 10.1016/j.jaut.2019.01.012. Epub 2019 Feb 8.
Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients.
T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cytometry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by immunohistochemistry. This study prospectively included 44 adult patients with biopsy-proven IgAV and 24 age- and sex-matched healthy controls.
We observed reduced proportions of circulating CXCR5-and CXCR3-expressing memory CD4 T cells at diagnosis but normal values at remission. The plasma levels of Th1-related cytokines (IL-12, IL-27 and IFNγ) and of the TFH-related cytokine, IL-21, were paradoxically not reduced in patients. We observed increased plasma concentrations of the CXCR5 ligand, CXCL13, and of the CXCR3 ligands, CXCL10/11, suggesting a potential relocation of the corresponding T cells into inflamed tissues. We then confirmed the recruitment of CXCR3-expressing T cells into the skin and kidneys. In the skin, T-cell infiltrates mainly co-localized with damaged dermal small vessels. Finally, patients with the largest kidney T-cell infiltrates were also those with the highest proteinuria.
Altogether, our results strongly suggest that, in IgAV patients, CXCL10/11 orchestrate the recruitment of CXCR3-expressing T cells in injured tissues, contributing to tissue damage and disease activity.
成人免疫球蛋白 A 血管炎（IgAV）是一种免疫复合物性小血管血管炎。到目前为止，T 细胞在此病理过程中的作用还研究得很少。本研究旨在分析 IgAV 患者血液和组织中的 T 细胞稳态以及细胞因子和趋化因子浓度。
使用流式细胞术和多重分析检测外周血中的 T 细胞、细胞因子和趋化因子浓度。通过免疫组织化学分析肾脏和皮肤中的 T 细胞浸润。本研究前瞻性纳入 44 例经活检证实的 IgAV 成年患者和 24 名年龄和性别匹配的健康对照者。
我们在诊断时观察到循环 CXCR5 和 CXCR3 表达记忆 CD4 T 细胞比例降低，但在缓解时正常。Th1 相关细胞因子（IL-12、IL-27 和 IFNγ）和 TFH 相关细胞因子 IL-21 的血浆水平在患者中并未降低。我们观察到 CXCR5 配体 CXCL13 和 CXCR3 配体 CXCL10/11 的血浆浓度升高，提示相应的 T 细胞可能向炎症组织重新定位。我们随后证实了 CXCR3 表达 T 细胞向皮肤和肾脏的募集。在皮肤中，T 细胞浸润主要与受损的真皮小血管共存。最后，肾脏 T 细胞浸润最大的患者也有最高的蛋白尿。
综上所述，我们的研究结果强烈表明，在 IgAV 患者中，CXCL10/11 协调 CXCR3 表达 T 细胞在受损组织中的募集，导致组织损伤和疾病活动。
