2. Academic Validation
  3. Inhibition of the type I interferon receptor pathway protects against muscle weakness induced by dermatomyositis serum

Inhibition of the type I interferon receptor pathway protects against muscle weakness induced by dermatomyositis serum

  • Ann Rheum Dis. 2026 Mar 17:S0003-4967(26)00096-8. doi: 10.1016/j.ard.2026.02.018.
Suchada Kaewin 1,  Cecilia Leijding 1,  Stefano Gastaldello 1,  David Makari 1,  Yi Zhong 2,  Kristofer M Andreasson 3,  Kent Jardemark 1,  Maryam Dastmalchi 4,  Begum Horuluoglu 5,  Helene Alexanderson 3,  Volker M Lauschke 6,  Ingrid E Lundberg 4,  Daniel C Andersson 7
Affiliations

Affiliations

  • 1 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • 2 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • 3 Department of Medicine, Solna, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Women's Health and Allied Health Professionals Theme, Medical Unit Allied Health Professionals, Stockholm, Sweden.
  • 4 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Solna, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden; Department of Gastro, Dermatology and Rheumatology, Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden.
  • 5 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Solna, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden.
  • 6 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tübingen, Tübingen, Germany; Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, China.
  • 7 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Heart, Vascular and Neurology Theme, Cardiology Unit, Karolinska University Hospital, Stockholm, Sweden. Electronic address: daniel.c.andersson@ki.se.
PMID: 41850941 DOI: 10.1016/j.ard.2026.02.018
Abstract

Objectives: Dermatomyositis (DM) is characterised by systemic inflammation, debilitating muscle weakness, cutaneous lesions, and increased mortality. An upregulation of type I interferon (IFN)-stimulated genes is observed in patients with DM. However, it remains unclear whether type I IFNs cause muscle weakness in DM. This study aimed to investigate the role of IFN-α/β receptor signalling in muscle weakness induced by factors in DM serum.

Methods: In ex vivo experiments, flexor digitorum brevis muscles were isolated from healthy mice and incubated 24 hours with 10% healthy serum or serum from patients with DM (n = 9). To modulate IFN signalling, an antibody against the type I IFN receptor α/β subunit 1 (IFNAR1) or the Janus kinase-signal transducer and activator of transcription inhibitor ruxolitinib was used. RNA Sequencing, followed by bioinformatics analysis, was conducted to identify differentially expressed genes and affected pathways related to IFN signalling.

Results: Incubation with serum from patients with DM, but not that from healthy controls, caused significant muscle weakness manifested by a reduction in muscle force. Bioinformatic analyses revealed downregulation of type I IFN-inducible genes with IFNAR1 antibody. Pathway analysis showed enrichment of several IFN-related pathways. Inhibition of type I IFN signalling with either an IFNAR1 antibody or ruxolitinib abolished DM serum-induced effects.

Conclusions: Factors in serum from patients with DM can activate the type I IFN signalling pathway in skeletal muscles, which constitutes an important causal factor for muscle weakness. Our data support a mechanistic model where blood-borne factors contribute to muscle disease phenotypes and underscore the therapeutic possibilities of pharmacological interventions targeting the IFNAR1 signalling pathway.

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