Defining the Langerhans cell precursor niche within the follicular microenvironment

• Applicant: Dr. Thomas Döbel
• Subject Area: Dermatology ; Immunology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257648705

Despite the importance of the organism's outermost barrier for the integrity of the host our understanding of skin immunity is still far from being complete. Langerhans cells are specialized cells of the skin immune system that reside within the epidermis and serve important immunological functions. They are able to sample the surface of the organism through intact tight junctions to confer a 'preemptive' Th2-mediated immunity before barriers are breached but also provide a Th17-mediated immunity after breaching of the barriers. Developmentally the epidermal Langerhans cell pool seems to be established by at least three different precursor cell populations: yolk sac macrophages of the primitive hematopoiesis, fetal monocytes of the early definitive hematopoiesis and after birth also bone marrow-derived monocytes. Bone marrow-derived monocytes seem to be especially important precursors after tissue stress and ablation of Langerhans cells. However, even after complete deletion of Langerhans cells bone marrow-independent langerin-negative precursors that are residing within hair follicles provide replenishment of the Langerhans cell pool. The aim of the project is the identification and characterization of the langerin-negative Langerhans cell precursor within the hair follicle and the characterization of the microenvironment that regulates its maintenance and differentiation. The identification of this langerin-negative Langerhans cell precursor will be guided by a fate-mapping approach based on cross-bred transgenic mice that will allow its isolation and in-depth characterization. To define factors for the maintenance of the precursor niche transcriptomes of hair-follicle keratinocyte subsets will be obtained followed by selection of candidate genes with potential regulatory capacity. The effects of the selected candidate genes will subsequently be analyzed in additional cross-bred mouse strains.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Keisuke Nagao, Ph.D.