蘭格素Langerin (CD207) 所媒介的過敏性發炎反應在異位性皮膚炎之研究

Abstract

Atopic dermatitis (AD) is characterized by hyperkeratosis of epidermis and fibrosis within dermis in chronic skin lesions. Thus far, the histology of skin lesions has been evaluated only by examination of excised specimens. We used Cr:forsterite laser-based multi-modality nonlinear microscopy to analyze the endogenous molecular signals, including third-harmonic generation (THG), second-harmonic generation (SHG), and two-photon fluorescence (TPF) from skin lesions in AD. Significant differences in thickness of epidermis and stratum corneum (SC) and modified degrees of fibrosis in dermis (measured by THG signals and SHG signals, respectively) were clearly demonstrated in in vitro studies. Increased TPF levels were positively associated with the levels of the THG signals from the SC. These findings were reproducible in skin lesions from human AD. Our findings suggest that the optical signatures of THG, TPF, & SHG can be used as molecular markers to assess the pathophysiological process of AD and the effects of local treatment. It remains unclear that CD207 of Langerhans cells (LCs) play a central role in the development of allergic sensitization. We used a murine model of epicutaneous (EC) ovalbumin (OVA) sensitization inducing an inflammatory skin resembling AD to explore the role of CD207 in the pathogenesis of AD. Cr:forsterite laser-based multi-modality nonlinear microscopy was applied for in situ imaging. Peritoneal injections of Alexa Fluor 647-rat anti-mouse CD207 into mice were performed to specifically trace the LCs. Peritoneal injections of OVA-Alexa Fluor 647 conjugate into mice were performed to specifically trace the OVA. We found that combining Alexa Fluor fluorescent probes with multi-modality nonlinear microscopy permitted the unequivocal in situ imaging of CD207-expressing LCs. The relevant time-course, expressional and functional studies revealed that CD207 of LCs play an essential role during the induction of EC sensitization. It’s suggested that CD207-expressing LCs initiate the allergic response through the CD207 mediated EC sensitization associated with the development of AD. AD patients show increased total serum IgE levels. The anti-IgE therapy has only limited efficacy in treating AD so that a prerequisite role of Langerhans cell (LC) in the development of AD were explored. We induced an animal model of AD by epicutaneous sensitization with ovalbumin (OVA). Peritoneal injection of blocking mAb against CD207 was given before epicutaneous sensitization and serum level of total IgE and skin histology were analyzed. The levels of total IgE and the epidermal thickness from mice group received blocking mAb were significantly reduced than those did not. The levels of plasma IL-4 and OVA-specific IgE in response to OVA sensitization in sensitized mice treated with blocking mAb anainst CD207 in vivo was lower than that from mice without blocking treatment. Our studies demonstrated that CD207 antagonists could attenuate allergic inflammation. We suggest that OVA uptake process associated with CD207 might contribute to the allergic response and play a role in the pathogenesis of AD.