With our current view of alopecia areata as an autoimmune disease, it is probable that disease development in an individual is dependent on multiple genetic and environmental factors interacting in a complex system. Rodent models afford the opportunity to investigate alopecia areata development and to define the significance of the different factors involved. Recently, rodent model characterization has been conducted using flow cytometry, microarray analysis, and functional studies. From these a pattern of events in alopecia areata development has emerged. Although the preliminary activation events for the onset of alopecia areata remain unknown, the response of the immune system is characterized by antigen presentation and costimulation of lymphocytes in the lymph nodes and skin, a deficiency of CD4+/CD25+ regulatory cells, and an action of activated lymphocytes on hair follicles via Fas/FasL signaling and cytokines. Thus, onset of disease may require appropriate (or inappropriate) expression of stimulatory antigens within the hair follicle, the breakdown of the putative hair follicle immune privilege, the presentation of antigens to the immune system, a failure of immune system regulation, and the ability of the activated immune system to disrupt anagen-stage hair follicles. Once the sequence of events is initiated, it may become a self-perpetuating cycle, with epitope spreading leading to a wider range of targets in chronic alopecia areata. Rodent model studies have provided significant insight into alopecia areata, but much more remains to be explained about the mechanisms of disease development.
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