title: IL-17/Th17 pathway is activated in acne lesions.
abstract: 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.
authors.affiliation: Department of Dermatology, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Hanna-Leena
authors.initials: HL
authors.lastname: Kelhälä
authors.affiliation: Department of Dermatology, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Palatsi
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Nanna
authors.initials: N
authors.lastname: Fyhrquist
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Lehtimäki
authors.affiliation: Department of Pathology, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Juha P
authors.initials: JP
authors.lastname: Väyrynen
authors.affiliation: Department of Pathology, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Kallioinen
authors.affiliation: Department of Dermatology, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Minna E
authors.initials: ME
authors.lastname: Kubin
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Dario
authors.initials: D
authors.lastname: Greco
authors.affiliation: Department of Dermatology, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Tasanen
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.affiliation: Research, Galderma R&D, Sophia Antipolis, France.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bertino
authors.affiliation: Research, Galderma R&D, Sophia Antipolis, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carlavan
authors.affiliation: Research, Galderma R&D, Sophia Antipolis, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Mehul
authors.affiliation: Research, Galderma R&D, Sophia Antipolis, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Déret
authors.affiliation: Research, Galderma R&D, Sophia Antipolis, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Reiniche
authors.affiliation: Early Development, Galderma R&D, Sophia Antipolis, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Martel
authors.affiliation: Early Development, Galderma R&D, Sophia Antipolis, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Marty
authors.affiliation: Department of Dermatology and Allergy, Charite Universitätsmedizin, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
authors.affiliation: Research, Galderma R&D, Sophia Antipolis, France.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Voegel
authors.affiliation: Department of Dermatology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Lauerma
mesh_terms: D000152:Acne Vulgaris / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D056704:Adaptive Immunity; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D018925:Chemokines; D020381:Interleukin-17; D012313:RNA