Somatostatin Expression in Human Hair Follicles and Its Potential Role in Immune Privilege

Abstract

Immune privilege (IP) is believed to exist in the anagen hair follicle (HF). Studies have shown that downregulation of major histocompatibility complex Class I occurs and immunosuppressive factors are expressed in the HF bulb and bulge. However, demonstration and quantification of functional IP in HF cells are required. We examined the middle (sheath) and lower (bulb) portions of the human HF using quantitative real-time RT-PCR (qPCR), immunohistology, ELISA, in vitro coculture with peripheral blood mononuclear cells (PBMCs), and flow cytometry. We found that HF cells, relative to non-follicular epidermal cells, failed to promote allogeneic PBMC proliferation and CD4(+) and CD8(+) IFNγ production. By qPCR, we found significant downregulation of Class I and Class II HLA alleles in both the bulb and sheath, and upregulation of multiple immunoregulatory genes. It is noteworthy that somatostatin (SST) was significantly upregulated relative to epidermis. By immunohistochemistry, SST was most strongly expressed in the HF outer root sheath, and, by ELISA, cultured sheath cells secreted SST. PBMCs, cultured with stimulatory allogeneic epidermal cells and SST, secreted significantly less IFNγ than controls. Addition of SST antagonists to PBMCs cocultured with allogeneic HF cells increased IFNγ secretion. The data identify SST as a secretory factor potentially contributing to the HF IP repertoire.

Alopecia areata: a review of disease pathogenesis

“…These IP guardians include [24][25][26] transforming growth factor (TGF)-b, a-melanocyte-stimulating hormone (MSH), indoleamine-2,3-dioxygenase (IDO), protein red encoded by the IK gene (red/IK), interleukin (IL)-10, calcitonin gene-related peptide, insulinlike growth factor-1 and somatostatin. 24,29,[32][33][34][35] The downregulation of MHC-I eventually leads to macrophage inhibition and the resultant suppression of interferon (IFN)-c production. 33,36 Although the absence of MHC-I helps in maintaining the IP, it also poses a threat by activating natural killer (NK) cells ('missing self' phenomena).…”

Frontal fibrosing alopecia: reflections and hypotheses on aetiology and pathogenesis

“…Protection is achieved by downregulation of major histocompatibility complex (MHC) class I and β2 microglobulin in the bulb and bulge of the hair follicle epithelium, besides an augmented expression of a local immunosuppressive milieu. In physiological terms, the exact role of the HF IP remains somewhat unclear, although proposed theories have included the possibility of the crucial evolutionary benefit of ensuring mammals such as polar bears maintained their hair . Relative IP loss in anagen hair follicular epithelium is postulated to underlie the organ‐specific autoimmune disorder AA, where loss of relative IP leads to ectopic MHC class I expression and, as yet elusive, autoantigens trigger a CD8+ T‐cell‐mediated inflammatory process, microscopically seen as the classic peribulbar “swarm of bees” (Fig.…”

The role of lymphocytes in the development and treatment of alopecia areata

“…Secreted immune suppressors αMSH, IGF-1, and TGFβ are all expressed in hair follicles [40,51]. Studies also suggest pleiotropic secretory factors such as somatostatin may further help support hair follicle IP [52]. These factors could allow hair follicles to regulate immune cells in the surrounding vicinity in advance of actual contact with hair follicle tissues.…”