Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis

• Published in: PloS one 2013-01, Vol.8 (1), p.e51752
• Main Authors: Singh, Tej Pratap, Schön, Michael P, Wallbrecht, Katrin, Gruber-Wackernagel, Alexandra, Wang, Xiao-Jing, Wolf, Peter
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antibodies; Antibodies, Monoclonal - administration & dosage; Biology; CD4 antigen; Cloning; Cytokines; Dermatologic agents; Dermatology; Endothelial cells; Genetic engineering; Helper cells; Humans; Hyperplasia; Immune response; Immune system; Immunoglobulins; Infiltration; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Inflammatory diseases; Injection; Interleukin 17; Interleukin 9; Interleukin-17 - biosynthesis; Interleukin-9 - immunology; Interleukin-9 - metabolism; Interleukin-9 - pharmacology; Lesions; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Macrophages; Mast cells; Medical research; Medicine; Mice; Mice, Transgenic; Monocytes; mRNA; Neovascularization, Pathologic - chemically induced; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Pathogenesis; Patients; Peripheral blood mononuclear cells; Phenotype; Psoriasis; Psoriasis - drug therapy; Psoriasis - genetics; Psoriasis - immunology; Psoriasis - pathology; RNA; Skin; Skin - immunology; Skin - metabolism; Skin - pathology; Skin diseases; T cells; Th17 Cells - immunology; Th17 Cells - metabolism; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - immunology; Transgenic animals; Transgenic mice; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051752

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.