Schlottmann Frederik, Strauß Sarah, Vogt Peter Maria, Bucan Vesna
Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany.
Eur Burn J. 2025 Aug 21;6(3):47. doi: 10.3390/ebj6030047.
Secondary rejection remains a major obstacle in skin allografting. Some viruses, such as human herpesvirus and cytomegalovirus, evade immune detection through proteins like the unique short glycoprotein 11 (US11), which down-regulates major histocompatibility complex (MHC) class I expression. This study explores the use of recombinant US11 protein as a biopharmaceutical approach to reduce MHC-I expression and thus decrease alloreactivity in human primary keratinocytes.
Human keratinocytes were treated with recombinant US11 protein, and MHC-I expression was assessed via Western blot and flow cytometry. To evaluate immunomodulatory effects, US11-stimulated keratinocytes were co-cultured with peripheral blood mononuclear cells (PBMCs), and interferon-gamma (IFN-γ) levels were measured by ELISA. Additionally, ex vivo human skin tissue was stimulated with US11 to assess long-term MHC-I modulation.
US11 treatment significantly reduced MHC-I surface expression in keratinocytes. Co-cultures showed decreased IFN-γ secretion, indicating lower T cell activation. Human skin tissue stimulated with US11 exhibited reduced MHC-I expression after 7 days.
This proof-of-concept study suggests that recombinant US11 protein may serve as an effective biopharmaceutical to reduce keratinocyte immunogenicity. Further in vitro and in vivo studies are warranted to validate its potential for clinical application in skin transplantation.
二次排斥仍然是皮肤移植的主要障碍。一些病毒，如人类疱疹病毒和巨细胞病毒，通过独特短糖蛋白11（US11）等蛋白质逃避免疫检测，该蛋白可下调主要组织相容性复合体（MHC）I类表达。本研究探讨使用重组US11蛋白作为一种生物制药方法来降低MHC-I表达，从而降低人原代角质形成细胞的同种异体反应性。
用重组US11蛋白处理人角质形成细胞，并通过蛋白质免疫印迹法和流式细胞术评估MHC-I表达。为了评估免疫调节作用，将经US11刺激的角质形成细胞与外周血单核细胞（PBMC）共培养，并通过酶联免疫吸附测定法（ELISA）测量干扰素-γ（IFN-γ）水平。此外，用US11刺激体外人皮肤组织以评估长期MHC-I调节。
US11处理显著降低了角质形成细胞中MHC-I的表面表达。共培养显示IFN-γ分泌减少，表明T细胞活化降低。经US11刺激的人皮肤组织在7天后MHC-I表达降低。
这项概念验证研究表明，重组US11蛋白可能作为一种有效的生物药物来降低角质形成细胞的免疫原性。有必要进行进一步的体外和体内研究，以验证其在皮肤移植临床应用中的潜力。
