UBC Theses and Dissertations
The role of somatostatin expression in hair follicle immune privilege Breitkopf, Trisia
The hair follicle is a mini-organ, consisting of many different types and groups of cells, capable of frequent remodeling and cycles of growth. Immune privilege (IP) is believed to exist in the anagen growth stage of the hair follicle (HF). Previous studies using immunohistology have illustrated unique downregulation of major histocompatibility complex Class I in the HF bulb, as well as expression of immunosuppressive factors in the bulge region. However, quantitative studies and functional studies to clearly demonstrate IP in HF cells are required. My goal was to examine the middle (hair fiber and sheaths) and lower (bulb) portion of the human HF to identify a novel functional mechanism of IP. My hypothesis was that the bulb and the middle third of the hair follicle have functional immune privilege capabilities. In an in vitro experiment, I found that HF cells appeared to suppress histo-incompatible peripheral blood mononuclear cell (PBMC) IFN-gamma secretion relative to epidermal cells. I screened expression of IP-related genes in HFs relative to interfollicular epidermis by quantitative real-time RT-PCR. Briefly, I found significant downregulation of all Class I and Class II HLAs examined in the bulb and sheaths. There were also several genes coding for immunosuppressant secretory factors significantly upregulated in the sheath. Most notably, somatostatin (SST) was significantly upregulated in the sheath 5.9-fold and in the bulb 94.2-fold relative to non-follicular epidermis. This led me to investigate the hypothesis that SST contributes to IP in hair follicles. I found strong expression of SST in the outer root sheath by immunohistochemistry and significant secretion of SST from HF sheath cells compared to epidermal cells in culture. PBMCs cultured with allogeneic immuno-stimulatory epidermal cells and SST secreted significantly less IFN-gamma than controls. Additionally, a SST antagonist drug appeared to interfere with the immunosuppressive effect of sheath cells in culture with allogeneic PBMCs. In summary, these experiments give further evidence in support of HF IP and show that HF bulb or sheath cells may be beneficial in allogeneic transplantation. In principle, SST may have potential as a treatment for scarring alopecia or other inflammatory hair loss disorders.
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