OPN functions in the skin immune system

骨桥蛋白(OPN)由免疫细胞表达，参与获得性免疫和获得性免疫的调节。我们证实了OPN在变态反应性接触性皮炎(ACD)及其小鼠接触性超敏模型(CHS)中的作用，在该模型中，OPN通过作用于树突状细胞(DC)和效应T细胞来支持Th1驱动的免疫，并由角质形成细胞分泌。最近，我们对ACD/CHS的看法发生了变化：新的重要皮肤DC亚群被发现调节致敏。先天免疫机制被证明是启动致敏的机制，ACD被认为具有重要的Th17成分。由于OPN增强先天免疫并支持Th17驱动的自身免疫，我们推测OPN在这一系统中发挥着重要作用。我们已经建立了转基因小鼠模型来研究OPN如何调节CHS的先天和获得性免疫功能。在致敏过程中，我们将探索OPN功能如何影响不同的皮肤DC亚群，以及当天然免疫机制被激活时，OPN-IL17轴如何塑造过敏原致敏。在过敏反应中，我们将研究OPN如何稳定Th17介导的炎症，并可能影响终止炎症的调节性T细胞。拟议的研究将加强我们对接触性超敏反应机制的了解，并可能为治疗ACD开辟新的治疗方法。

Osteopontin (OPN) is expressed by immune cells and participates in the modulation of both adaptive and acquired immunity. We demonstrated functions for OPN in allergic contact dermatitis (ACD) and its murine contact hypersensitivity model (CHS), where OPN supports Th1 driven immunity through effects on dendritic cells (DC) and effector T cells and is se-creted by keratinocytes. Recently our perception of ACD/CHS has changed: New important skin DC subsets were found to modulate sensitization. Innate immune mechanisms were demonstrated to initiate sensitization and ACD was recognized to have an important Th17 component. Because OPN enhances innate immunity and supports Th17 driven autoimmu-nity we hypothesize that OPN is an important player in this system. We have established transgenic mouse models to investigate, how OPN modulates innate and adaptive immune functions in CHS. During sensitization we will explore, how OPN functions influence different skin DC subsets and how the OPN-IL17 axis shapes allergen sensitization when innate immune mechanisms are activated. During allergic response we will investigate, how OPN stabilizes Th17 mediated inflammation and may influence regulatory T cells that terminate inflammation. The proposed investigations will strengthen our knowledge on the mechanisms of contact hypersensitivity and may open new therapeutic approaches for treating ACD.