The Contributory Roles of Th17 Lymphocyte and Cytotoxic T Lymphocyte at the Hair Bulge Region as Well as the Hair Bulb Area in the Chronic Alopecia Areata Patients

BACKGROUND Alopecia areata (AA) is a T cell-mediated autoimmune disease that targets hair follicles and interrupts hair regrowth. The microenvironment of the effector T cells and their related cytokines may affect immunopathogenesis around the hair bulb/bulge. OBJECTIVE To determine the contributory roles of the effector T cell subsets and related cytokines to the pathogenesis of AA. METHODS We investigated the correlation between histopathological grades and four clinical prognostic factors in 331 patients with AA, and analyzed the topography of T cell infiltrates and related cytokines around the hair bulb/bulge according to histopathological grades through immunohistochemical and double immunofluorescence studies on a subset of AA specimens. RESULTS First, the groups with more severe histopathological grades were associated with earlier onset, longer duration, more hair loss, as well as poorer therapeutic outcomes. Second, the pattern of CD4 and CD8 expression around the hair bulb/bulge varied by histopathological grade, with staining density decreasing in the following order: type 1>type 2>type 3. In addition, interferon-γ and transforming growth factor-β1 expression appeared denser in the peribulbar area. Interestingly, the denser CCR6+ cells (Th17 cells) showed more infiltration than CCR5+ cells (Th1 cells) around the hair bulb/bulge as histopathological grade worsened. CONCLUSION The insidious destruction of bulge stem cells and hair bulb matrix stem cells results in more severe hair loss in patients with chronic AA, which is mediated by Th17 lymphocyte and cytotoxic T lymphocyte infiltration. Furthermore, Th17 lymphocytes may play an even more important role than cytotoxic T cells in the development of AA.