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Updated: Jan 12, 2026

Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
The exacerbating role of Ras guanyl-releasing protein 1 in idiopathic inflammatory myopathies
Marina Kise1, Miku Shimamura1, Natsuka Umezawa1
1Department of Rheumatology, Graduate School of Medical and Dental Science, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
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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