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

最近，我们证实了表达膜糖蛋白CD4的小鼠表皮细胞的存在（Uhmann， A, et al.），在PtchCD4Cre小鼠中，DMBA/ tpa处理对于补丁缺陷表皮细胞形成BCC是必要的。J投资皮肤，2014。这些细胞在角质形成细胞标记CD49f（整合素- 6）以及干细胞标记CD34和Sca1 （Ly6a，淋巴细胞抗原6复合物，位点A）上也呈阳性。此外，CD4+表皮细胞中肿瘤抑制基因patch （Ptch）纯合子缺失的小鼠在DMBA（7,12-二甲基苯[a]-蒽）/TPA （12- o - tetradecanoylphorbol13 -acetate）化学处理后发生基底细胞癌（BCC）。此外，我们能够验证人体皮肤中CD4+ CD49fhigh细胞的存在。这些细胞对皮肤基底层标记物（CD29和角蛋白15）染色呈阳性，但对CD3、CD1a或CD14染色呈阴性。因此，我们的数据表明，人类皮肤的CD4+细胞不是造血细胞，而是迄今为止未知的细胞群（未发表的数据）。因此，我们将通过进行分子分析，体外培养分析以及移植实验和实时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，因此计划对该主题进行研究。因此，我们将对CD4+表皮细胞中CD4的信号转导能力进行分析。此外，它将检查CD4+表皮细胞是否可能在皮肤癌的发展中发挥作用，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。

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data show that CD4+ cells of the human skin are not hematopoietic cells but represent a so far unknown cell population (unpublished data).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.