130 Characterization of neutrophil activation from blood to blister in experimental epidermolysis bullosa acquisita by single-cell transcriptomics
نویسندگان
چکیده
Epidermolysis bullosa acquisita (EBA) is an autoimmune disease caused by autoantibodies against collagen 7. In the inflammatory form, these fix complement and induce neutrophil influx, subsequently leading to inflammation at basement membrane zone. To better understand activation of neutrophils in blood how correspond with lesional neutrophils, we performed single-cell RNA sequencing skin from passive transfer EBA mice controls. Dimensionality reduction analysis cells identified a unique population group consistent activated neutrophils. Bioinformatic gating was then isolate based onbona fide putative markers, resolution decreased consider as single for each condition. Wilcoxon Rank Sum Test revealed 148 upregulated 375 downregulated genes between basal (P-adjusted < 0.05). We likewise S100A8/S100A9/Ly6G positive mice, but not Neutrophils were aligned pseudospace. Trajectory tissue notable upregulation numerous members C-type lectin-like domain (CTL/CTLD) superfamily. Expression CLEC4D, CLEC4E, CLEC4N on confirmed immunofluorescent staining. have developed novel workflow allow study granulocyte infiltration into skin, identifying several key markers CTL/CTLD superfamily potentially targetable molecules particularly intradermal
منابع مشابه
The alternative pathway of complement activation is critical for blister induction in experimental epidermolysis bullosa acquisita.
Epidermolysis bullosa acquisita is a subepidermal blistering disease associated with tissue-bound and circulating autoantibodies against type VII collagen, a major constituent of the dermal-epidermal junction. The passive transfer of Abs against type VII collagen into mice induces a subepidermal blistering disease dependent upon activation of terminal complement components. To further dissect t...
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متن کاملT cells are required for the production of blister-inducing autoantibodies in experimental epidermolysis bullosa acquisita.
Epidermolysis bullosa acquisita is a prototypical organ-specific autoimmune disease caused by autoantibodies against type VII collagen of the dermal-epidermal junction. Although mechanisms of autoantibody-induced blister formation were extensively characterized, the initiation of autoantibody production in autoimmune blistering diseases is still poorly defined. In the current study, we addresse...
متن کاملEpidermolysis bullosa acquisita: what's new?
Type VII collagen is an adhesion molecule of the extracellular matrix in epithelial basement membranes, and the main constituent of anchoring fibrils at the dermal-epidermal junction (DEJ). Autoimmunity against this protein is causing the rare organ-specific epidermolysis bullosa acquisita (EBA). EBA is a rare acquired, heterogeneous, chronic blistering disease of skin disease of skin and mucou...
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.131