title: Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin.
abstract: OBJECTIVE
  To characterise global chemokine expression in systemic sclerosis (SSc) skin in order to better understand the relationship between chemokine expression and vascular inflammation in this disease.
  
  
  METHODS
  We investigated chemokine mRNA expression in the skin through quantitative PCR analysis comparing patients with diffuse cutaneous (dcSSc) or limited cutaneous (lcSSc) disease with healthy controls. We tested correlations between the most regulated chemokines and vascular inflammation and macrophage recruitment. CCL19 expression was examined in human primary immune cells treated with innate immune activators.
  
  
  RESULTS
  The chemokines, CCL18, CCL19 and CXCL13, were upregulated in dcSSc skin, and CCL18 in lcSSc skin. Expression of CCL19 in dcSSc skin correlated with markers of vascular inflammation and macrophage recruitment. Immunofluorescence data showed CCL19 colocalisation with CD163 macrophages in dcSSc skin. In vitro studies on human primary cells demonstrated that CCL19 expression was induced after toll-like receptor activation of peripheral blood mononuclear cells and separated populations of CD14 monocytes.
  
  
  CONCLUSIONS
  CCL18, CCL19 and CXCL13-chemoattractants for macrophage and T cell recruitment-were three of six chemokines with the highest expression in dcSSc skin. Increased CCL19 expression in the skin suggests a role for CCL19 in the recruitment of immune cells to the peripheral tissue. Induction of CCL19 in macrophages but not structural cells indicates a role for skin-resident or recruited immune cells in perivascular inflammation. This study demonstrates that CCL19 is a sensitive marker for the perivascular inflammation and immune cell recruitment seen in dcSSc skin disease.
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Mathes
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Romy B
authors.initials: RB
authors.lastname: Christmann
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Stifano
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Alsya J
authors.initials: AJ
authors.lastname: Affandi
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: G Alessandra
authors.initials: GA
authors.lastname: Farina
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Padilla
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: McLaughlin
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lafyatis
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology; D017445:Skin Diseases, Vascular / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D014657:Vasculitis / Q000209:etiology / Q000235:genetics / Q000276:immunology*
chemical_list: D015415:Biomarkers; C515460:CCL19 protein, human; D054415:Chemokine CCL19; D018925:Chemokines; D012333:RNA, Messenger
keywords: Chemokines; Inflammation; Systemic Sclerosis