Activated Dendritic Cell Subsets Characterize Muscle of Inclusion Body Myositis Patients and Correlate with KLRG1+ and TBX21+ CD8+ T cells
Kirou, R. A.; Pinal-Fernandez, I.; Casal-Dominguez, M.; Pak, K.; Ikenaga, C.; Nelke, C.; Wischnewski, S.; Del Orso, S.; Naz, F.; Islam, S.; Gutierrez-Cruz, G.; Lloyd, T. E.; Schirmer, L.; Ruck, T.; Stenzel, W.; Selva-O'Callaghan, A.; Milisenda, J. C.; Mammen, A. L.
Show abstract
Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy characterized by muscle-infiltrating KLRG1+ and TBX21+ cytotoxic T cells and type 1 inflammation. Myeloid dendritic cells (mDCs), including type 1 conventional dendritic (cDC1) cells, type 2 conventional dendritic (cDC2) cells, and mature immunoregulatory dendritic (mregDC) cells, have previously been reported in skeletal muscle of IBM patients and may activate these cytotoxic T cells. Here, we analyzed single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (RNA-seq) data from skeletal muscle of IBM, other myositis, and control patients to identify and quantify these mDC subsets and characterize their contribution to IBM inflammation. Our findings reveal that all three mDC subsets are relatively increased and activated in muscle of IBM patients and correlate with IBM-specific inflammatory markers. Our data specifically implicates cDC1 cells in CD8+ T cell activation via specific expression of both KLRG1 ligands, CDH1 and CDH2, as well as IL12B in IBM muscle.
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