Regulatory T cells in skin lesions and blood of patients with bullous pemphigoid

Background: Although regulatory T cells (Tregs) are affected in several autoimmune skin diseases, only two studies have been performed in patients with bullous pemphigoid (BP) with contrasting results. Objective: To characterize Tregs and to determine the serum levels of regulatory cytokines in patients with BP. Methods: In BP lesional skin, immunohistochemistry and confocal microscopy were performed for CD4+, CD25+, forkhead/winged helix transcription factor (FOXP3)+, transforming growth factor (TGF)-β+ and interleukin (IL)-10+ cells. In addition, the number of CD4+CD25++FOXP3+ Tregs in peripheral blood was assessed by flow cytometry, and the levels of TGF-β and IL-10 were determined in serum samples by enzyme-linked immunosorbent assay before and after steroid therapy. Controls included patients with psoriasis, atopic dermatitis (AD) and healthy donors. Results: The frequency of FOXP3+ cells was significantly reduced in skin lesions from patients with BP (P < 0.001) compared with psoriasis and AD. Moreover, the number of IL-10+ cells was lower in BP than in psoriasis (P < 0.001) and AD (P = 0.002), while no differences were observed in the number of TGF-β+ cells. CD4+CD25++FOXP3+ Treg in the peripheral blood of patients with BP was significantly reduced compared with healthy controls (P < 0.001), and augmented significantly after steroid therapy (P = 0.001). Finally, TGF-β and IL-10 serum levels were similar in patients with BP compared with healthy controls. However, after therapy, BP patients showed significantly higher IL-10 serum levels than before therapy (P = 0.01). Conclusions: These data suggest that the depletion of Tregs and of IL-10 in patients with BP may be an important factor in the pathogenesis of the disease.