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In morphea, cytotoxic resident memory T cells induce chronic, immunogenic endothelial cell injury via necroptosis
William J. Crisler, Noor Sohail, Samuel J. Steuart, Maria Vazquez-Machado, Arjun Mahajan, Maureen Whittelsey, Alex Pickering, Michael J. Martinez, Theresa Hutchins, Jessica E. Teague, Qian Zhan, Shannan Ho Sui, Ruth Ann Vleugels, Kathryn S. Torok, Heidi Jacobe, Rachael A. Clark, Avery LaChance
William J. Crisler, Noor Sohail, Samuel J. Steuart, Maria Vazquez-Machado, Arjun Mahajan, Maureen Whittelsey, Alex Pickering, Michael J. Martinez, Theresa Hutchins, Jessica E. Teague, Qian Zhan, Shannan Ho Sui, Ruth Ann Vleugels, Kathryn S. Torok, Heidi Jacobe, Rachael A. Clark, Avery LaChance
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Research Letter Dermatology Immunology

In morphea, cytotoxic resident memory T cells induce chronic, immunogenic endothelial cell injury via necroptosis

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Abstract

Authors

William J. Crisler, Noor Sohail, Samuel J. Steuart, Maria Vazquez-Machado, Arjun Mahajan, Maureen Whittelsey, Alex Pickering, Michael J. Martinez, Theresa Hutchins, Jessica E. Teague, Qian Zhan, Shannan Ho Sui, Ruth Ann Vleugels, Kathryn S. Torok, Heidi Jacobe, Rachael A. Clark, Avery LaChance

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Figure 1

Cytotoxic Trm induce endothelial injury and necroptosis in morphea skin lesions.

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Cytotoxic Trm induce endothelial injury and necroptosis in morphea skin ...
(A–F) Single-cell RNA-seq (scRNA-Seq) studies from lesions of adult morphea (n = 13) and healthy skin (HS) (n = 8) biopsies showing major skin cell populations (A), T cell counts and frequencies (B), T cell and NK cell subsets (C), cytotoxic gene expression across T cell subsets in morphea (D), endothelial cell (EC) subsets (E), and differentially expressed genes (F) in pooled vascular ECs from morphea versus HS. (G) CellChat analysis predicted TNF ligand-receptor interactions among all cell populations in morphea, with thicker lines indicating stronger interaction strength; only significant interactions are shown. (H) Postcapillary venule ECs are reduced in morphea, with a relative increase of other venular endothelial cells. (I) Multiplex immunofluorescence shows apoptotic (cleaved-caspase-3+) ECs (CD31+) adjacent to CD3+ T cells in morphea, with quantification per 200× high-power field (HPF) shown. (J and K) Representative morphea images show necroptotic (pMLKL+) ECs near CD3+CD8+ cytotoxic T cells (J) and CD3+CD69+ or CD3+CD103+ tissue-resident T cells (K), with corresponding quantification per 200× HPF versus HS. Insets: arrowheads indicate T cells; arrows indicate apoptotic (I) or necroptotic (J and K) ECs. Scale bars: 50 μm. Bars represent individual donors; data are shown as mean ± SEM of 3 independent measurements. Statistical significance for immunostaining was determined by nested 2-tailed t tests; for box plots, by 2-tailed unpaired t tests.

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