Auflistung nach Autor:in "Guo, Sen"

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Multi-omics analysis uncovers split formation and keratinocyte detachment as key drivers of long-lasting cellular effects in pemphigus vulgaris
(2025-08-11) Guo, Sen
Pemphigus Vulgaris (PV) is an autoimmune disease in which antibodies mistakenly target the adhesion proteins Desmoglein 1 (DSG1) and/or Desmoglein 3 (DSG3) on skin cells, leading to the loss of cell-cell adhesion and causing blistering. While the molecular changes following antibody binding in PV remain poorly understood, we investigated these downstream effects by analyzing gene and protein responses in two experimental models: human primary epidermal keratinocytes (HPEKs) and human skin organ culture (HSOC). Samples were treated with either PX43, a human-derived antibody fragment targeting DSG1 and DSG3, or AK23, a mouse-derived DSG3 antibody, alongside control treatments. In the HPEK model, PV antibody treatments did not trigger notable changes compared to controls at 5, 10, or 24 hours. However, in the HSOC model, only PX43 induced tissue splitting and significant changes in gene and protein expression, particularly in pathways linked to inflammation and immune signaling (e.g., TNFα, Interferon α/γ, IL2-STAT5, IL5-STAT3). Importantly, these molecular changes resembled those seen in wounded or inflamed skin, suggesting that physical damage from blister formation—not the antibody binding itself—is the primary driver of downstream cellular responses. This study reveals that tissue injury may be the main trigger for disease progression in PV, pointing toward new therapeutic targets that focus on modulating the wound response and inflammation, rather than the antibodies alone.