title: Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis.
abstract: It is thought that a Th1/Th17-weighted immune response plays a predominant role in the pathogenesis of psoriasis. Our findings now indicate a link between IL-9, a Th2 and Th9 cytokine, and Th17 pathway in psoriasis. In K5.hTGF-β1 transgenic mice, exhibiting a psoriasis-like phenotype, we found increased IL-9R and IL-9 expression in the skin and intradermal IL-9 injection induced Th17-related inflammation. IL-9 also promoted angiogenesis and VEGF and CD31 overexpression in mice in vivo and increased tube formation of human endothelial cells in vitro. Injecting anti-IL-9 antibody into K5.hTGF-β1 transgenic mice not only diminished inflammation (including skin infiltration by T cells, monocytes/macrophages, and mast cells) and angiogenesis but also delayed the psoriasis-like skin phenotype. Notably, injection of anti-psoriatic acting anti-IL-17 antibody reduced skin IL-9 mRNA and serum IL-9 protein levels in K5.hTGF-β1 transgenic mice and prevented IL-9-induced epidermal hyperplasia and inflammation of the skin of wild type mice. In addition, we observed that IL-9R expression in lesional skin from psoriasis patients was markedly higher than in healthy skin from control subjects. Moreover, IL-9 significantly enhanced IL-17A production by cultured human peripheral blood mononuclear cells or CD4+ T cells, especially in psoriasis patients. Thus, IL-9 may play a role in the development of psoriatic lesions through Th17-associated inflammation and angiogenesis.
authors: Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria.
authors: Tej Pratap
authors: TP
authors: Singh
authors: Michael P
authors: MP
authors: Schön
authors: Katrin
authors: K
authors: Wallbrecht
authors: Alexandra
authors: A
authors: Gruber-Wackernagel
authors: Xiao-Jing
authors: XJ
authors: Wang
authors: Peter
authors: P
authors: Wolf
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis; D016906:Interleukin-9 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D016906:Interleukin-9; D053773:Transforming Growth Factor beta1