Dataset Information

Imaging Mass Cytometry Reveals Predominant Innate Immune Signature and Endothelial-Immune Cell Interaction in Juvenile Myositis Compared to Lupus Skin.

ABSTRACT:

Objective

Cutaneous inflammation can signal disease in juvenile dermatomyositis (DM) and childhood-onset systemic lupus erythematosus (cSLE), but we do not fully understand cellular mechanisms of cutaneous inflammation. In this study, we used imaging mass cytometry to characterize cutaneous inflammatory cell populations and cell-cell interactions in juvenile DM as compared to cSLE.

Methods

We performed imaging mass cytometry analysis on skin biopsy samples from juvenile DM patients (n = 6) and cSLE patients (n = 4). Tissue slides were processed and incubated with metal-tagged antibodies for CD14, CD15, CD16, CD56, CD68, CD11c, HLA-DR, blood dendritic cell antigen 2, CD20, CD27, CD138, CD4, CD8, E-cadherin, CD31, pan-keratin, and type I collagen. Stained tissue was ablated, and raw data were acquired using the Hyperion imaging system. We utilized the Phenograph unsupervised clustering algorithm to determine cell marker expression and permutation test by histoCAT to perform neighborhood analysis.

Results

We identified 14 cell populations in juvenile DM and cSLE skin, including CD14+ and CD68+ macrophages, myeloid and plasmacytoid dendritic cells (pDCs), CD4+ and CD8+ T cells, and B cells. Overall, cSLE skin had a higher inflammatory cell infiltrate, with increased CD14+ macrophages, pDCs, and CD8+ T cells and immune cell-immune cell interactions. Juvenile DM skin displayed a stronger innate immune signature, with a higher overall percentage of CD14+ macrophages and prominent endothelial cell-immune cell interaction.

Conclusion

Our findings identify immune cell population differences, including CD14+ macrophages, pDCs, and CD8+ T cells, in juvenile DM skin compared to cSLE skin, and highlight a predominant innate immune signature and endothelial cell-immune cell interaction in juvenile DM, providing insight into candidate cell populations and interactions to better understand disease-specific pathophysiology.

SUBMITTER: Turnier JL

PROVIDER: S-EPMC9771877 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Imaging Mass Cytometry Reveals Predominant Innate Immune Signature and Endothelial-Immune Cell Interaction in Juvenile Myositis Compared to Lupus Skin.

Turnier Jessica L JL Yee Christine M CM Madison Jacqueline A JA Rizvi Syed M SM Berthier Celine C CC Wen Fei F Kahlenberg J Michelle JM

Arthritis & rheumatology (Hoboken, N.J.) 20221018 12

<h4>Objective</h4>Cutaneous inflammation can signal disease in juvenile dermatomyositis (DM) and childhood-onset systemic lupus erythematosus (cSLE), but we do not fully understand cellular mechanisms of cutaneous inflammation. In this study, we used imaging mass cytometry to characterize cutaneous inflammatory cell populations and cell-cell interactions in juvenile DM as compared to cSLE.<h4>Methods</h4>We performed imaging mass cytometry analysis on skin biopsy samples from juvenile DM patient ...[more]

PMID: 35762881

Similar Datasets

Project description:ObjectiveSkin inflammation heralds systemic disease in juvenile myositis, yet we lack an understanding of pathogenic mechanisms driving skin inflammation in this disease. We undertook this study to define cutaneous gene expression signatures in juvenile myositis and identify key genes and pathways that differentiate skin disease in juvenile myositis from childhood-onset systemic lupus erythematosus (SLE).MethodsWe used formalin-fixed paraffin-embedded skin biopsy samples from 15 patients with juvenile myositis (9 lesional, 6 nonlesional), 5 patients with childhood-onset SLE, and 8 controls to perform transcriptomic analysis and identify significantly differentially expressed genes (DEGs; q ≤ 5%) between patient groups. We used Ingenuity Pathway Analysis (IPA) to highlight enriched biologic pathways and validated DEGs by immunohistochemistry and quantitative real-time polymerase chain reaction.ResultsComparison of lesional juvenile myositis to control samples revealed 221 DEGs, with the majority of up-regulated genes representing interferon (IFN)-stimulated genes. CXCL10, CXCL9, and IFI44L represented the top 3 DEGs (fold change 23.2, 13.3, and 13.0, respectively; q < 0.0001). IPA revealed IFN signaling as the top canonical pathway. When compared to childhood-onset SLE, lesional juvenile myositis skin shared a similar gene expression pattern, with only 28 unique DEGs, including FBLN2, CHKA, and SLURP1. Notably, patients with juvenile myositis who were positive for nuclear matrix protein 2 (NXP-2) autoantibodies exhibited the strongest IFN signature and also demonstrated the most extensive Mx-1 immunostaining, both in keratinocytes and perivascular regions.ConclusionLesional juvenile myositis skin demonstrates a striking IFN signature similar to that previously reported in juvenile myositis muscle and peripheral blood. Further investigation into the association of a higher IFN score with NXP-2 autoantibodies may provide insight into disease endotypes and pathogenesis.

Dataset Information

Imaging Mass Cytometry Reveals Predominant Innate Immune Signature and Endothelial-Immune Cell Interaction in Juvenile Myositis Compared to Lupus Skin.

Objective

Methods

Results

Conclusion

Publications

Imaging Mass Cytometry Reveals Predominant Innate Immune Signature and Endothelial-Immune Cell Interaction in Juvenile Myositis Compared to Lupus Skin.

Similar Datasets

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