A 'hairy' privilege

Understanding how selected tissue sites establish immune privilege (IP) is of interest to both basic immunology and clinical medicine: it provides novel insights into autoimmunity, fetal and allotransplant rejection and tumor escape from immunosurveillance. Here, we review why the hair follicle can serve as a uniquely accessible, widely available and instructive model for studying the establishment, maintenance, collapse and restoration of IP. The hair follicle epithelium rhythmically generates, maintains and deconstructs an area of relative IP, characterized by very low expression of MHC Ia and suppressed MHC II-dependent antigen presentation, accompanied by the local production of potent immunosuppressants capable of downregulating MHC I (e.g. transforming growth factor-beta1, alpha-melanocyte-stimulating hormone). We discuss the physiological functions of hair follicle IP, illustrate its clinical and therapeutic relevance by focusing on alopecia areata, an autoimmune hair loss disorder, and outline important unanswered questions for future research into one of nature's most intriguing and abundant, yet commonly ignored, sites of IP.