TGF beta 1 was initially identified as a potent chemotactic cytokine to initiate inflammation, but the autoimmune phenotype seen in TGF beta 1 knockout mice reversed the dogma of TGF beta 1 being a pro-inflammatory cytokine to predominantly an immune suppressor. The discovery of the role of TGF beta 1 in Th17 cell activation once again revealed the pro-inflammatory effect of TGF beta 1. We developed K5. TGF beta 1 mice with latent human TGF beta 1 overexpression targeted to epidermal keratinocytes by keratin 5. These transgenic mice developed significant skin inflammation. Further studies revealed that inflammation severity correlated with switching TGF beta 1 transgene expression on and off, and genome wide expression profiling revealed striking similarities between K5. TGF beta 1 skin and human psoriasis, a Th1/Th17-associated inflammatory skin disease. Our recent study reveals that treatments alleviating inflammatory skin phenotypes in this mouse model reduced Th17 cells, and antibodies against IL-17 also lessen the inflammatory phenotype. Examination of inflammatory cytokines/chemokines affected by TGF beta 1 revealed predominantly Th1-, Th17-related cytokines in K5. TGF beta 1 skin. However, the finding that K5. TGF beta 1 mice also express Th2-associated inflammatory cytokines under certain pathological conditions raises the possibility that deregulated TGF beta signaling is involved in more than one inflammatory disease. Furthermore, activation of both Th1/Th17 cells and regulatory T cells (Tregs) by TGF beta 1 reversely regulated by IL-6 highlights the dual role of TGF beta 1 in regulating inflammation, a dynamic, context and organ specific process. This review focuses on the role of TGF beta 1 in inflammatory skin diseases.
[1]Univ Colorado Denver, Dept Pathol, Aurora, CO 80045 USA.
[2]Shanghai Univ Tradit Chinese Med, Dept Dermatol, Yueyang Hosp Integrated Tradit Chinese & Western, Shanghai, Peoples R China.
[3]Med Univ Graz, Dept Dermatol, Res Unit Photodermatol, Graz, Austria.
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