Involvement of T cells in early evolving segmental vitiligo

Recent studies have suggested an overlapping autoimmune mechanism between segmental vitiligo (SV) and nonsegmental vitiligo (NSV). Although T‐cell infiltration is observed in the margins of active lesions in NSV, the histopathological characteristics of the active margin of SV are not well known. To determine if T‐cell inflammatory responses are present in the active margin of SV lesions, biopsies were taken from the active margin of a lesion in 12 patients with early or actively spreading SV and compared with a normal control sample (on the symmetrical, opposite site of the same dermatome). The samples were stained for CD4, CD8, CD25 and interferon‐γ. Lymphocytic infiltration was seen in 70% of patients. CD4+ T cells infiltrated the dermis, while CD8+ T cells were present in the epidermis or attached to the basal layer. The increase in the number of CD8+ T cells was significant (P < 0.04), while CD4+ or CD25+ T cells also appeared to be increased in number, but this was not significant. These results suggest that SV also has an autoimmune mechanism in the early evolving stage.     

TWEAK/Fn14 activation induces keratinocyte proliferation under psoriatic inflammation

Tumor necrosis factor (TNF)‐like weak inducer of apoptosis (TWEAK) has been reported to induce keratinocyte apoptosis in vitro by engaging its sole receptor of fibroblast growth factor‐inducible 14 (Fn14). In this study, we explored the role of TWEAK/Fn14 pathway in the growth of psoriatic keratinocytes that is, however, characterized by suppressed apoptotic cell death. Skin tissues from the patients with psoriasis or healthy donors were determined for TWEAK and Fn14 expression, and primary keratinocytes were evaluated under the stimulation of psoriatic proinflammatory cytokines or plus TWEAK. The results showed that both TWEAK and Fn14 were highly expressed in psoriatic skins. Moreover, the stimulation of psoriatic cytokines enhanced Fn14 expression by keratinocytes in vitro, which expressed TNF receptor 2 predominantly and proliferated increasingly with the addition of TWEAK. Furthermore, TWEAK stimulation enhanced the synthesis of survivin, inhibitor of apoptosis protein 2 and cellular FLICE‐inhibitory protein in lesional keratinocytes. Therefore, TWEAK/Fn14 interaction prefers to enhance proliferation but not apoptosis of keratinocytes under psoriatic inflammation. The activation of nuclear factor‐κB signalling‐dependent anti‐apoptotic proteins and biased expression of TNF receptors may be responsible for such a novel principle in keratinocytes under psoriatic inflammation.