Characterization of CD4+ stem cell-like epidermal cells and their role during wound healing processes, tumorigenesis and as a possible HIV reservoir

CD4 干细胞样表皮细胞的特征及其在伤口愈合过程、肿瘤发生和可能的 HIV 储存库中的作用

• 批准号: 356030054
• 负责人: Privatdozentin Dr. Anja Uhmann
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/356030054?language=en
• 关键词: Characterization; CD4+; stem; cell; like

Recently we demonstrated the existence of murine epidermal cells that express the membrane glycoprotein CD4 (Uhmann, A., et al., DMBA/TPA-Treatment is Necessary for BCC Formation from Patched Deficient Epidermal Cells in PtchCD4Cre Mice. J Invest Dermatol, 2014.). These cells also stained positive for the keratinocyte marker CD49f (integrin alpha 6) as well as for the stem cell markers CD34 and Sca1 (Ly6a, lymphocyte antigene 6 complex, locus A). Moreover mice that harbors a homozygous deletion of the tumor suppressor gene Patched (Ptch) in CD4+ epidermal cells develop basal cell carcinoma (BCC) upon chemical treatment with DMBA (7,12-dimethylbenz[a]-anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate). Additionally we were able to verify the existence of CD4+ CD49fhigh cells in the human skin. These cells stain positive for markers of the basal layer of the skin (CD29 and keratin 15) but are negative for CD3, CD1a or CD14. Thus our data show that CD4+ cells of the human skin are not hematopoietic cells but represent a so far unknown cell population (unpublished data). Therefore we will characterize this CD4+ epidermal cell population by conducting molecular analyses, in vitro culture assays as well as transplantation experiments and live-imaging methods. Moreover since the function of the CD4 protein in CD4+ epidermal cells is not known it is planned to investigate this topic. Therefore analyses of the signal transduction capacity of CD4 in CD4+ epidermal cells will be conducted. Additionally it will be examined if CD4+ epidermal cells might play a role in the development of skin cancer and might be susceptible and permissive for Human Immunodeficiency Virus (HIV) and therefore might represent a HIV reservoir.

最近，我们证明了表达膜糖蛋白CD4的鼠表皮细胞的存在（Uhmann，A.，例如，DMBA/TPA-处理对于PtchCD4Cre小鼠中从补丁缺陷表皮细胞形成BCC是必需的。J Invest Dermatol，2014.）。这些细胞也对角质形成细胞标志物CD49f（整联蛋白α 6）以及干细胞标志物CD34和Sca 1（Ly6a，淋巴细胞抗原6复合物，基因座A）染色呈阳性。此外，在CD4+表皮细胞中具有肿瘤抑制基因Patched（Ptch）的纯合缺失的小鼠在用DMBA（7，12-二甲基苯并[a]-蒽）/TPA（12-O-十四烷酰基佛波醇-13-乙酸酯）化学处理后发生基底细胞癌（BCC）。此外，我们能够证实人皮肤中存在CD4 + CD49fhigh细胞。这些细胞对皮肤基底层的标志物（CD29和角蛋白15）染色呈阳性，但对CD3、CD1a或CD14呈阴性。因此，我们的数据表明，人皮肤的CD4+细胞不是造血细胞，而是迄今未知的细胞群（未发表的数据）。因此，我们将通过进行分子分析、体外培养测定以及移植实验和活体成像方法来表征这种CD4+表皮细胞群。此外，由于CD4蛋白在CD4+表皮细胞中的功能尚不清楚，因此计划研究该主题。因此，将对CD4+表皮细胞中CD4的信号转导能力进行分析。此外，还将检查CD4+表皮细胞是否可能在皮肤癌的发生中发挥作用，是否可能对人类免疫缺陷病毒（HIV）易感和允许，因此可能代表HIV储存库。