OPN functions in the skin immune system

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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.