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

• Applicant: Privatdozentin Dr. Anja Uhmann
• Subject Area: Dermatology ; Cell Biology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 356030054

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show that CD4+ cells of the human skin are not hematopoietic cells but represent a so far unknown cell population (unpublished data).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

• DFG Programme: Research Grants