No abstract

Green fluorescent protein (GFP)-expressing wild-type, and nontransgenic mouse vibrissa follicle cells were cultured and implanted to mouse ears and footpads. Dermal papiller (DP)-derived cells and cells from the peribulbar dermal sheath "cup" (DSC) induced new hair follicles in both implanted ears and footpads, while nonbulbar dermal sheath cells did not. Confocal microscopy revealed that GFP-expressing DP and DSC cells induced hair growth associated with the formation of DP exclusively comprised of fluorescent cells. In mouse ears, but not footpads, fluorescent DP and DSC cells could also be identified in DP along with nonfluorescent cells. DSC cells were characterized in vivo and in vitro by low alkaline phosphatase activity in contrast to high alkaline phosphatase in DP cells. The results indicate transplanted DP and DSC cells were equally capable of DP formation and hair follicle induction. This suggests the DP and peribulbar DSC may be functionally similar. In addition to observing papillae exclusively composed of GFP-expressing cells, DP and DSC cells may also have combined with resident cells to form papillae composed of implanted GFP-expressing cells and host-derived non-GFP-expressing cells. Alkaline phosphatase expression may be utilized as a simple marker to identify hair follicle mesenchyme derived cells with hair follicle inductive abilities.

Frontal fibrosing alopecia is increasingly seen in postmenopausal women and rarely in men. Despite the limitations of a retrospective study, we conclude early intervention and treatment with intralesional triamcinolone acetonide may halt the progression of the disease; however, further controlled prospective studies are needed to establish treatment guidelines for frontal fibrosing alopecia.

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8+ T cells, CD4+ T cells and NKGD2+ NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA-related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re-evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease.

Alopecia areata (AA)-like hair loss in C3H/HeJ mice provides an excellent model for human AA disease research. The potential to induce mouse AA in normal haired C3H/HeJ mice at an early age or serially passage the AA phenotype was investigated by exchange of full-thickness skin grafts. Skin grafts from normal male and female C3H/HeJ, or severe combined immunodeficient C3H/SmnC Prkdc(scid)/J, mice onto AA-affected C3H/HeJ mice became inflamed and lost hair (28 of 28). Successful grafts from AA-affected C3H/HeJ mice induced hair loss in histocompatible C3H/OuJ mice (four of 13) and normal C3H/HeJ mice dependent on age (four of 17 at <31 d and 15 of 15 at >70 d). The AA phenotype was serially transmitted from induced AA mice to normal C3H/HeJ mice (nine of nine). Grafts from AA-affected C3H/HeJ mice onto C3H/SmnC Prkd(scid)/J mice resulted in depigmented hair fiber regrowth and perifollicular neutrophil and eosinophil infiltrates but no hair loss (15 of 15). Sham grafting did not induce AA (none of 10). The finding that AA can be serially transferred from AA-affected C3H/HeJ mice to normal littermates and C3H/ OuJ mice, indicates that an immune response against hair follicles can be induced with suitable stimuli. Conversely, skin grafts from normal C3H/HeJ, or C3H/SmnC Prkd(scid)/J, mice rapidly lose hair due to lymphocyte, but not neutrophil and eosinophil, mediated inflammation. This AA induction method reproducibly provides large numbers of AA-affected mice to study the pathogenesis and treatment of human AA.