title: The pro-inflammatory role of TGFβ1: a paradox?
abstract: TGFβ1 was initially identified as a potent chemotactic cytokine to initiate inflammation, but the autoimmune phenotype seen in TGFβ1 knockout mice reversed the dogma of TGFβ1 being a pro-inflammatory cytokine to predominantly an immune suppressor. The discovery of the role of TGFβ1 in Th17 cell activation once again revealed the pro-inflammatory effect of TGFβ1. We developed K5.TGFβ1 mice with latent human TGFβ1 overexpression targeted to epidermal keratinocytes by keratin 5. These transgenic mice developed significant skin inflammation. Further studies revealed that inflammation severity correlated with switching TGFβ1 transgene expression on and off, and genome wide expression profiling revealed striking similarities between K5.TGFβ1 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 TGFβ1 revealed predominantly Th1-, Th17-related cytokines in K5.TGFβ1 skin. However, the finding that K5.TGFβ1 mice also express Th2-associated inflammatory cytokines under certain pathological conditions raises the possibility that deregulated TGFβ signaling is involved in more than one inflammatory disease. Furthermore, activation of both Th1/Th17 cells and regulatory T cells (Tregs) by TGFβ1 reversely regulated by IL-6 highlights the dual role of TGFβ1 in regulating inflammation, a dynamic, context and organ specific process. This review focuses on the role of TGFβ1 in inflammatory skin diseases.
authors.affiliation: Department of Pathology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Gangwen
authors.initials: G
authors.lastname: Han
authors.forename: Fulun
authors.initials: F
authors.lastname: Li
authors.forename: Tej Pratap
authors.initials: TP
authors.lastname: Singh
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D053773:Transforming Growth Factor beta1