Peer-reviewed veterinary case report
The exacerbating role of Ras guanyl-releasing protein 1 in idiopathic inflammatory myopathies.
- Journal:
- Clinical immunology (Orlando, Fla.)
- Year:
- 2026
- Authors:
- Kise, Marina et al.
- Affiliation:
- Department of Rheumatology · Japan
- Species:
- rodent
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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Search related cases →Original publication: https://pubmed.ncbi.nlm.nih.gov/41197821/