Induction of antigen specific peripheral tolerance by targeting Langerhans cells

点击翻译按钮获取中文摘要

Phototherapy generally induces a relatively long remission period in patients with psoriasis, which cannot be explained simply by UV-induced apoptosis. Therefore, the role of regulatory T cells should also be considered. We recently reported that narrow-band UVB suppresses delayed-type hypersensitivity (DTH) and contact hypersensitivity by inducing regulatory T cell production. The UV wavelength that induced regulatory T cells to DTH, however, was not known. We irradiated a mouse DTH model using a monochromator to produce several UVB wavelengths (290 nm, 300 nm, 310 nm, and 320 nm). All wavelengths tested significantly suppressed DTH, with 300 nm inducing maximal suppression. Foxp3 expression in lymph node cells from tolerant mice was analyzed by real time polymerase chain reaction (mRNA) and FACS analysis (protein). Foxp3 induction was increased 2-fold at 300 nm compared with controls. Similarly, interleukin (IL)-10 induction was increased 10-fold at 300 nm. Conversely, IL-17, IL-23, and IL-12 were suppressed by 40%, 25%, and 30%, respectively, at 300 nm. These data indicate that 300-nm UV light induces Foxp3-expressing regulatory T cells and suppresses Th-17 cells. Besides inducing Foxp3-expressing regulatory T cells, the suppression of Th-17 cells might be important for the UV light-induced immune suppression. The use of a specific wavelength within the UVB range is a new strategy for the induction of antigen-specific peripheral tolerance and provides a new potential treatment for allergic dermatologic diseases.