Leboit P E, Patel D U, Cohen J N, Moss M I, Naik H B, Yates A E, Harris H W, Klufas D M, Kim E A, Neuhaus I M, Hansen S L, Kyle R L, Kelly M, Rosenblum M D, Lowe M M
bioRxiv. 2024 Jul 23:2024.07.19.603617. doi: 10.1101/2024.07.19.603617.
Hidradenitis Suppurativa (HS) is a relatively common and highly morbid inflammatory skin disease. Due to our relatively limited understanding of HS's pathogenesis, there are currently insufficient treatment options available, and many patients' medical needs are not being met. This is partly due to a scarcity of ex vivo human assays and animal models that accurately recapitulate the disease. To address this deficit, we have developed a whole-tissue explant model of HS to examine its pathogenic mechanisms and the efficacy of potential treatments within intact human tissue. We measured cytokine protein and RNA within whole tissue maintained in an agar-media solution, finding that IL-6 and IL-8 concentrations trended upwards in both HS explants and healthy controls, while IL-17A, IL-1β, and TNF-α exhibited increases in HS tissue alone. We also show that the explants were responsive to treatment with both dexamethasone and IL-2. Not only do our results show that this model effectively delivers treatments throughout the explants, but they also elucidate which cytokines are related to the explant process regardless of tissue state and which are related to HS tissue specifically, laying the groundwork for future implementations of this model.
化脓性汗腺炎(HS)是一种相对常见且具有高度致病性的炎症性皮肤病。由于我们对HS发病机制的了解相对有限,目前可用的治疗选择不足,许多患者的医疗需求未得到满足。部分原因是缺乏能够准确重现该疾病的体外人体检测方法和动物模型。为了弥补这一不足,我们开发了一种HS全组织外植体模型,以研究其致病机制以及在完整人体组织中潜在治疗方法的疗效。我们测量了琼脂培养基溶液中全组织内的细胞因子蛋白和RNA,发现HS外植体和健康对照中IL-6和IL-8浓度均呈上升趋势,而IL-17A、IL-1β和TNF-α仅在HS组织中升高。我们还表明,外植体对地塞米松和IL-2治疗均有反应。我们的结果不仅表明该模型能有效地将治疗药物输送到整个外植体,还阐明了哪些细胞因子与外植过程相关而与组织状态无关,哪些细胞因子与HS组织特异性相关,为该模型的未来应用奠定了基础。