IL-17/Th17 Pathway Is Activated in Acne Lesions

• Published in: PloS one Vol. 9; no. 8; p. e105238
• Main Authors: Kelhälä, Hanna-Leena, Palatsi, Riitta, Fyhrquist, Nanna, Lehtimäki, Sari, Väyrynen, Juha P., Kallioinen, Matti, Kubin, Minna E., Greco, Dario, Tasanen, Kaisa, Alenius, Harri, Bertino, Beatrice, Carlavan, Isabelle, Mehul, Bruno, Déret, Sophie, Reiniche, Pascale, Martel, Philippe, Marty, Carine, Blume-Peytavi, Ulrike, Voegel, Johannes J., Lauerma, Antti
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.08.2014; Public Library of Science (PLoS)
• Subjects: Acne; Acne Vulgaris - genetics; Acne Vulgaris - immunology; Acne Vulgaris - pathology; Adaptive Immunity; Antimicrobial peptides; Biology and Life Sciences; Biomarkers - metabolism; Biopsy; CCL20 protein; CD83 antigen; Cell activation; Cell Differentiation; Cell Lineage; Chemokines; Chemokines - genetics; Chemokines - metabolism; CXCR3 protein; Cytokines; Dendritic cells; Dermatology; Foxp3 protein; Gene expression; Gene Expression Regulation; Gram-positive bacteria; Helper cells; Hospitals; Humans; Immunity; Immunohistochemistry; Inflammation; Innate immunity; Interleukin 1; Interleukin 10; Interleukin 17; Interleukin 6; Interleukin 8; Interleukin-17 - metabolism; Lesions; Lipocalin; Lymphocytes; Lymphocytes T; Markers; Medical research; Medicine and Health Sciences; Neutrophils; Occupational health; Pathogenesis; Peptides; Polymerase chain reaction; Propionibacterium acnes; Psoriasis; R&D; Research & development; Ribonucleic acid; RNA; RNA - metabolism; Skin; Skin diseases; Th17 Cells - metabolism; Toxicology; Transcriptome; Tumor necrosis factor-α; γ-Interferon; France; Germany; Finland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0105238

The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy.