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Spatial Transcriptomics Identifies Immune-Stromal Niches Associated with Cancer in Adult Dermatomyositis.
Ksenia S Anufrieva1, Neda Shahriari2, Ce Gao1
1Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Biorxiv : the Preprint Server for Biology
|April 1, 2025
Summary
Adult-onset dermatomyositis (DM) skin lesions show distinct immune cell patterns. Cancer-associated DM has dispersed immune cells, while non-cancer DM exhibits dense myeloid infiltrates impacting vascular health.
Area of Science:
- Immunology
- Dermatology
- Genomics
Background:
- Adult-onset dermatomyositis (DM) is an autoimmune disease characterized by muscle inflammation and unique skin rashes.
- DM has a significant association with underlying malignancies.
- Understanding the cellular microenvironment in DM skin is crucial for diagnosis and treatment.
Purpose of the Study:
- To perform an integrated spatial and single-cell transcriptomics analysis of adult-onset DM skin lesions.
- To compare immune and stromal niches in DM with cutaneous lupus erythematosus (CLE).
- To identify unique cellular and molecular signatures associated with cancer-associated versus non-cancer-associated DM.
Main Methods:
- Integrated spatial and single-cell transcriptomics analysis.
- Comparative analysis between DM and CLE skin lesions.
- Identification and characterization of immune cell infiltrates and stromal components.
Main Results:
- Distinct immune and stromal niches were identified in DM subtypes.
- Cancer-associated DM skin showed dispersed immune infiltrates (macrophages, CD8+ T cells, plasma cells, B cells) with preserved vasculature.
- Non-cancer DM skin exhibited dense myeloid infiltrates (neutrophils, monocytes, macrophages) with elevated IL1B and CXCL10, leading to stromal remodeling and vascular-associated fibroblast loss.
- Specific cellular pairs (PD-L1+ mregDCs and activated Tregs) emerged in non-cancer DM with pDC presence.
- DM uniquely displayed IFN-β expression, alongside shared interferon signatures with CLE.
Conclusions:
- This study provides the first comprehensive spatial map of immune and stromal cells in adult-onset DM.
- Unique cellular signatures differentiate cancer-associated from non-cancer-associated DM, offering potential diagnostic biomarkers.
- The findings highlight the role of myeloid-derived cytokines and tissue hypoxia in driving DM pathogenesis and stromal changes.
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