Document Type

Article

Publication Date

2-18-2026

Abstract

Objective: Dysregulated type I interferon (IFN) signaling contributes to autoimmune myositis pathogenesis. We investigated the therapeutic effects of JAK inhibitors in two mouse models. We also examined how type I IFNs affect muscle vasculature. Methods: Myositis was induced in MHC class I transgenic (HT) female mice at day 21. Mice were randomized into four groups (n=10-11/group): baricitinib (10 mg/kg), tofacitinib (20 mg/kg), vehicle, and healthy controls. Outcomes included survival, weight, muscle strength, histopathology, and IFN stimulated gene expression. To model IFNβ overexpression, C57BL/6 mice received AAV9-tMCK-IFNβ and were treated with vehicle or tofacitinib (40 mg/kg/day) for 10 weeks (n=8-13/group). Results: Tofacitinib—but not baricitinib—significantly reduced IFN scores in severe myositis mice (p< 0.05). Survival differed across groups (overall log-rank p< 0.01), with untreated- and baricitinib-treated HT mice showing shorter survival than BL/6 controls, while tofacitinib-treated mice did not differ from controls. IFNβ overexpression induced muscle inflammation (p< 0.01), reduced grip strength (p< 0.0001), and increased the IFN score (p< 0.0001) and H2Kb (p< 0.0001) expression. Conclusion: Tofacitinib reduced the IFN signature, and survival in this group did not differ significantly from healthy controls, whereas untreated- and baricitinib-treated HT mice showed shorter survival; functional improvement was not observed. Our results also show that type I IFN signaling contributes to muscle inflammation and weakness, making it a key driver of muscle damage and thereby reinforcing its potential as a therapeutic target.

Comments

https://doi.org/10.1002/art.70096

Publisher Attribution

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/art.70096. This article is protected by copyright. All rights reserved. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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