Aberrant overexpression of the autoantigen protein vimentin promotes Th17 cell differentiation and autoimmune arthritis via activation of STAT3 signaling

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2024-10-23 DOI:10.1016/j.clim.2024.110383

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引用次数: 0

Abstract

Vimentin contributes to the positioning and function of organelles, cell migration, adhesion, and division. However, secreted vimentin accumulates on the cell surface (Mor-Vaknin et al., 2003; Ramos et al., 2020 [1,2]) where it acts as a coreceptor for viral infection and as an autoantigen in inflammatory and autoimmune diseases. The roles of vimentin in Th17 cells were examined in mice with knockdown of vimentin. We also examined whether STAT3 is required for vimentin expression.

Vimentin expression was significantly increased in Th17 cells through STAT3 activation, and vimentin⁺ IL-17⁺ T cells were markedly increased in the joint and spleen tissues of CIA mice. The arthritis score and expression levels of proinflammatory cytokines were significantly decreased in CIA mice treated with vimentin shRNA vector.

In this study, we demonstrated that vimentin is significantly expressed in Th17 cells through STAT3 activation. Our results provide new insights into the role of vimentin in Th17 cells and the complex pathogenesis of RA.

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自身抗原蛋白波形蛋白的过量表达会通过激活 STAT3 信号促进 Th17 细胞分化和自身免疫性关节炎。

波形蛋白有助于细胞器的定位和功能、细胞迁移、粘附和分裂。然而，分泌的波形蛋白会积聚在细胞表面（Mor-Vaknin 等人，2003 年；Ramos 等人，2020 年 [1,2]），在病毒感染中充当核心受体，在炎症和自身免疫性疾病中充当自身抗原。我们在敲除波形蛋白的小鼠中研究了波形蛋白在 Th17 细胞中的作用。我们还研究了波形蛋白的表达是否需要 STAT3。通过STAT3激活，Th17细胞中的波形蛋白表达明显增加，CIA小鼠的关节和脾脏组织中波形蛋白+ IL-17+ T细胞明显增加。用vimentin shRNA载体治疗的CIA小鼠的关节炎评分和促炎细胞因子的表达水平明显下降。在这项研究中，我们证实了波形蛋白通过 STAT3 激活在 Th17 细胞中显著表达。我们的研究结果为了解波形蛋白在Th17细胞中的作用以及RA复杂的发病机制提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.