The Role of Hair Follicle Immune Privilege Collapse in Alopecia Areata: Status and Perspectives

Abstract

Alopecia areata (AA) may represent a CD8+T cell-mediated, organ-specific autoimmune disease in which as yet elusive autoantigens are recognized, once they become exposed by ectopic major histocompatibility complex class I expression by anagen hair follicles (HFs) that have lost their relative immune privilege (IP). On this basis, AA research is chiefly challenged with identifying the autoreactive CD8+T cells and their cognate autoantigens as well as key inducers of HF-IP collapse and "HF-IP guardians" that prevent and/or can restore IP collapse. However, natural killer group 2D-positive (NKG2D+) cells (incl. NK, NKT, and CD8+T cells) and NKG2D-activating ligands from the MICA (MHC I-related chain A) family may also have a key role in AA pathogenesis, as a massive infiltrate of IFN-γ-secreting NKG2D+ cells alone suffices to induce the AA phenotype. Therefore, we speculate that AA may represent a stereotypic, but distinct HF response pattern to inflammatory insults associated with HF-IP collapse.

Alopecia areata

“…Under normal physiological conditions a local immune-inhibitory signaling milieu in and around the hair follicle is generated that suppresses the surface molecules required for presenting autoantigens to NK cells, including CD8 + T lymphocytes. Although the function (or functions) of this hair follicle immune privilege are not proven 71–74 , it is believed that several autoantigens that are related with pigment production in melanocytes are immunogenic and, under the right circumstances, can result in loss of immune privilege 75 .…”

Special Stains and Immunohistochemical Stains in Hair Pathology

“…19 Several hair loss disorders outlined below have been associated with MCs. [20][21][22][23][24][25][26][27][28][29] Currently, these findings are of scientific value without direct diagnostic application to practice.…”

“…23 Substance P and interferon gamma are implicated as the most important inducers of the collapse of the immune privilege of the hair follicle in AA. 24 Recently, Bertolini et al 22 showed that not only are MCs increased in lesional AA biopsies from human and mouse skin but they also interact with the CD8 + T cells, thus promoting their pathogenic responses against hair follicles. the vertex in men with AGA when compared with the vertex of men with normal hair density.…”

Erosive Pustular Dermatosis: A Manifestation of Immunosenescence A Report of 8 Cases

“…Hair follicles with their characteristic low-surface major histocompatibility complex (MHC) are classified as an immune privilege site, a title mainly attributed to several vital organs including the brain, testes, and cornea [20]. EPD may have an association with other autoimmune diseases [1,21].…”