Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders.

The 2011 Cicatricial Alopecia Symposium** * was attended by approximately 90 members of the scientific community representing academia, industry, and government. The program was held over 2 days and included three keynote talks and six sessions: (i) Bench: “Mechanisms of inflammation”; (ii) Bedside: “Disease Presentation and Epidemiology”; (iii) Bench: “Nuclear Receptors and Lipids in Skin and Hair Disease”; (iv) Bedside: “Current and Emerging Therapies for Cicatricial Alopecia”; (v) Identifying Translational Opportunities in Cicatricial Alopecia; and (vi) Stem cells, Cicatricial Alopecia, and Hair Follicle Regeneration. In addition to major talks by invited speakers, the meeting included short talks selected from submitted abstracts, followed by panel discussions. The symposium culminated in a workshop composed of small discussion groups, each focusing on specific research questions and priorities.

The hair follicle is a sensing, reactive, dynamic and complex skin appendage that offers many essential functions and requires a specific molecular environment to remain fully functional. Apart from providing an insulating layer in animals, hair serves as an aid in camouflage for survival and provides sensory, tactile information about the environment. Hair may also be of importance in attracting mates by offering insight into an individual’s health and vitality through its color, distribution, or quality. Hair follicles are formed from epidermal-dermal interactions and modeling during the first trimester in humans. Hair growth is a unique and complex process that involves continuous cycles of growth, resorption, rest and renewal. The hair follicle is constantly exposed to the environment and suffers direct damage from the sun, the air, and water. Exposure to foreign chemicals may also cause damage to the hair shaft and follicle. There are numerous hair diseases and the hair follicle is involved in over a thousand systemic diseases including genetic disorders. The social function of hair is the foundation for a multibillion dollar industry focused on presenting, augmenting, preserving, or removing hair.