title: Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1/Th17 Pathways.
abstract: Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, quantitative real-time reverse-transcriptase-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from patients with facial lupus erythematosus and healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T-cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFN-γ or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T-cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, whereas neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for the activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern toward phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration are an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany; Charles Institute for Translational Dermatology, University College Dublin, Dublin, Ireland; Department of Dermatology and Surgery, University of California, San Francisco, California, USA.
authors.forename: Timo
authors.initials: T
authors.lastname: Buhl
authors.affiliation: Department of Dermatology and Surgery, University of California, San Francisco, California, USA; Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Sulk
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Pawel
authors.initials: P
authors.lastname: Nowak
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Buddenkotte
authors.affiliation: Charles Institute for Translational Dermatology, University College Dublin, Dublin, Ireland.
authors.forename: Ian
authors.initials: I
authors.lastname: McDonald
authors.affiliation: Molecular Dermatology, Research Department, Galderma R&D, Sophia Antipolis, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Aubert
authors.affiliation: Molecular Dermatology, Research Department, Galderma R&D, Sophia Antipolis, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carlavan
authors.affiliation: Molecular Dermatology, Research Department, Galderma R&D, Sophia Antipolis, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Déret
authors.affiliation: Molecular Dermatology, Research Department, Galderma R&D, Sophia Antipolis, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Reiniche
authors.affiliation: Molecular Dermatology, Research Department, Galderma R&D, Sophia Antipolis, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Rivier
authors.affiliation: Molecular Dermatology, Research Department, Galderma R&D, Sophia Antipolis, France. Electronic address: johannes.voegel@galderma.com.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Voegel
authors.affiliation: Charles Institute for Translational Dermatology, University College Dublin, Dublin, Ireland; Department of Dermatology and Surgery, University of California, San Francisco, California, USA; Department of Dermatology, University of San Diego, USA. Electronic address: martin.steinhoff@ucd.ie.
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology / Q000502:physiology*; D000328:Adult; D001707:Biopsy, Needle; D016022:Case-Control Studies; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D012016:Reference Values; D012393:Rosacea / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D018925:Chemokines
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