The exacerbating role of Ras guanyl-releasing protein 1 in idiopathic inflammatory myopathies

IF 4.1 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2026-01-01 Epub Date: 2025-11-04 DOI:10.1016/j.clim.2025.110636

Marina Kise , Miku Shimamura , Natsuka Umezawa , Nao Tanaka , Rihan Da , Shiyao Li , Tadashi Hosoya , Tetsuya Saito , Chikashi Terao , Shinsuke Yasuda

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引用次数: 0

Abstract

Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders characterized by muscle injury mediated by both T cells and macrophages. Ras guanyl-releasing protein 1 (RasGRP1) is a guanine exchange factor for a small G protein Ras, expressed in immune cells. In this study, we investigated the role of RasGRP1 in IIMs. RasGRP1 was expressed in either CD8+, CD4+ or CD68+ cells in muscles from IIM patients as well as a murine model of myositis, C protein-induced myositis (CIM). RasGRP1 expression was upregulated in activated CD8+ T cells and macrophages in vitro. Response to MHC Class I-restricted stimulation in Rasgrp1−/− CD8+ T cells was impaired. Furthermore, Rasgrp1−/− mice were resistant to CIM. Differentially expressed genes between Rasgrp1−/− and WT mice with CIM were enriched in both adaptive and innate immune responses. These results suggested that RasGRP1 could exacerbate myositis via both T cells and macrophages. RasGRP1 is a possible therapeutic target for IIMs.

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Ras鸟苷释放蛋白1在特发性炎性肌病中的加重作用。

特发性炎性肌病（IIMs）是一种以T细胞和巨噬细胞介导的肌肉损伤为特征的自身免疫性疾病。Ras鸟苷释放蛋白1 （RasGRP1）是免疫细胞中表达的小G蛋白Ras的鸟嘌呤交换因子。在本研究中，我们研究了RasGRP1在IIMs中的作用。RasGRP1在IIM患者肌肉中的CD8+、CD4+或CD68+细胞中表达，也在肌炎、C蛋白诱导的肌炎（CIM）小鼠模型中表达。在体外活化的CD8+ T细胞和巨噬细胞中，RasGRP1表达上调。Rasgrp1-/- CD8+ T细胞对MHC i类限制性刺激的反应受损。此外，Rasgrp1-/-小鼠对CIM具有耐药性。具有CIM的Rasgrp1-/-和WT小鼠之间的差异表达基因在适应性和先天免疫反应中都富集。这些结果表明RasGRP1可以通过T细胞和巨噬细胞加重肌炎。RasGRP1可能是IIMs的治疗靶点。

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.