Immunology of the hair follicle: a short journey into terra incognita.

This paper delineates briefly why the immunology of the hair follicle matters (e.g., anti-infection defense, hair growth control by immunomodulatory agents, sequestration of follicular autoantigens), and which open key questions await clarification. We then focus on the murine hair follicle immune system (HIS) and its immune privilege. We show how the murine HIS is gradually constructed during hair follicle morphogenesis, and how it is transformed during hair follicle cycling. Key characteristics of the HIS are summarized, such as the absence of MHC class I expression in the anagen hair bulb and the very restricted distribution of antigen-presenting cells and intraepithelial T cells to the distal outer root sheath, which also expresses nonclassical MHC class Ib molecules. The interconnections between the HIS and the skin immune system (SIS) and potential hair growth-modulatory roles of mast cells and macrophages are addressed, and very recent findings on the human HIS are summarized. The paper closes by sketching immunobiologic, clinical, and pharmacologic perspectives in trichoimmunology that deserve the attention of immunologists, dermatologists, and hair biologists alike.