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Myeloid dendritic cell subsets characterise muscle in patients with inclusion body myositis and correlate with the IFN-γ pathway and effector T cell markers: myositis

Objectives - Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy characterised by type 1 inflammation, driven by muscle-infiltrating KLRG1+ and TBX21+ cytotoxic T cells. However, the cellular sources of the stimuli that trigger this effector response in the muscle of patients with I...

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Main Authors: Kirou, Raphael A. (Author) , Pinal-Fernandez, Iago (Author) , Casal-Dominguez, Maria (Author) , Pak, Katherine (Author) , Ikenaga, Chiseko (Author) , Nelke, Christopher (Author) , Wischnewski, Sven (Author) , Preusse, Corinna (Author) , Del Orso, Stefania (Author) , Naz, Faiza (Author) , Islam, Shamima (Author) , Gutierrez-Cruz, Gustavo (Author) , Lloyd, Thomas E. (Author) , Schirmer, Lucas (Author) , Ruck, Tobias (Author) , Stenzel, Werner (Author) , Selva-O’Callaghan, Albert (Author) , Milisenda, Jose C. (Author) , Mammen, Andrew L. (Author)
Format: Article (Journal)
Language:English
Published: July 2026
In: Annals of the rheumatic diseases
Year: 2026, Volume: 85, Issue: 7, Pages: 1413-1424
ISSN:1468-2060
DOI:10.1016/j.ard.2026.03.001
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ard.2026.03.001
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0003496726001457
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Author Notes:Raphael A. Kirou, Iago Pinal-Fernandez, Maria Casal-Dominguez, Katherine Pak, Chiseko Ikenaga, Christopher Nelke, Sven Wischnewski, Corinna Preusse, Stefania Del Orso, Faiza Naz, Shamima Islam, Gustavo Gutierrez-Cruz, Thomas E. Lloyd, Lucas Schirmer, Tobias Ruck, Werner Stenzel, Albert Selva-O’Callaghan, Jose C. Milisenda, Andrew L. Mammen
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Summary:Objectives - Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy characterised by type 1 inflammation, driven by muscle-infiltrating KLRG1+ and TBX21+ cytotoxic T cells. However, the cellular sources of the stimuli that trigger this effector response in the muscle of patients with IBM remain unclear. Given their role as antigen-presenting cells, we hypothesised that these may be myeloid dendritic cells (mDCs), which have previously been reported in skeletal muscle of patients with IBM. We used immunohistochemistry, immunofluorescence, single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (RNA-seq) data from skeletal muscle of patients with IBM, other myositis, and controls to identify mDCs and characterise their contribution to IBM inflammation. - Methods - We first analysed snRNA-seq data from 3 datasets to identify, quantify, and characterise 3 mDC subsets: type 1 conventional dendritic (cDC1) cells, type 2 conventional dendritic (cDC2) cells, and mature immunoregulatory dendritic (mregDC) cells. We then analysed RNA-seq data from 2 datasets to correlate specific markers of these subsets with markers of IBM disease activity. We used immunohistochemistry and immunofluorescence to confirm mDC presence. - Results - All 3 mDC subsets, and especially cDC1 cells, are relatively increased in the muscle of patients with IBM and correlate strongly with IBM-specific inflammatory markers, including KLRG1 and TBX21. In particular, cDC1 cells specifically express the KLRG1 ligands, CDH1 and CDH2, and, along with mregDC cells, IL12B, representing possible juxtacrine and paracrine signals for effector T cells in IBM. - Conclusions - Skeletal muscle of patients with IBM is specifically characterised by mDC subsets that correlate with markers of cytotoxic T cells and type 1 inflammation.
Item Description:Online verfügbar: 6. Mai 2026, Artikelversion: 30. Juni 2026
Im Titel ist "gamma" bei "IFN-gamma" mit einem griechischen Buchstaben geschrieben
Gesehen am 11.08.2026
Physical Description:Online Resource
ISSN:1468-2060
DOI:10.1016/j.ard.2026.03.001

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