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Role of TGFβ1 in Cutaneous Inflammation

TGFβ1 is a well characterized immunosuppressive cytokine for many cells of the immune system, and growth inhibitor of normal skin keratinocytes.  Many chronic inflammatory states in the skin such as Psoriasis have elevated cutaneous and serum TGFβ1 levels, although the mechanism through which TGFβ1 could contribute to chronic inflammation is now known. We and others have shown that overexpression of TGFβ1 by keratinocytes in the mouse epidermis causes inflammation and epidermal hyperplasia, supporting a role for this cytokine in chronic inflammatory diseases.  We have recently showed that elevated TGFβ1 in the epidermis can cause activation and lymph node migration of several subsets of cutaneous dendritic cells and these activated dendritic cells drive an increased contact hypersensitivity response in the skin. In parallel TGFβ1 overexpression causes a major influx of inflammatory dendritic cells and plasmacytoid dendritic cells into the skin, which may play a role in driving chronic inflammation. Other studies ongoing in our lab show that UVB, the major etiological agent in human skin cancer, activates TGFβ1 signaling in the skin, and this is associated with lymphnode migration of dermal dendritic cells and activation of cutaneous inflammation.  Dendritic cells in which TGFβ1 signalign is blocked do not migrate to the lymph node. Our current studies are geared towards understanding how TGFβ1 causes activation, lymph node migration and skin infiltration of specific dendritic cell subsets and how this this is linked to chronic skin inflammation and skin cancer.