title: Platelets Induce Thymic Stromal Lymphopoietin Production by Endothelial Cells: Contribution to Fibrosis in Human Systemic Sclerosis.
abstract: To investigate the relationship between vascular damage and fibrosis in systemic sclerosis (SSc) by testing the hypothesis that platelets contribute to skin fibrosis via the activation of human dermal microvascular endothelial cells (HDMECs) and subsequent production of profibrotic mediators.
  
  
  
  A total of 203 SSc patients and 30 healthy donors were prospectively enrolled between 2012 and 2015 at the University Hospital of Bordeaux. Immunohistochemistry and immunofluorescence analyses were performed on skin biopsy sections from 18 SSc patients and 5 healthy donors. Serum thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay in the entire cohort. HDMECs and fibroblasts were purified from biopsy sections. Extracellular matrix production by cultured fibroblasts was assessed by real-time quantitative polymerase chain reaction.
  
  
  
  Serum TSLP levels were significantly increased in SSc patients compared to healthy donors (P < 0.0001) and were associated with a higher frequency of vasculopathy (P = 0.02). The proportion of TSLP-positive dermal cells was increased in the skin of SSc patients compared with healthy donors (P < 0.0001) and was correlated with fibrosis (modified Rodnan skin thickness score) (r = 0.6146, P = 0.0001). In SSc dermis, TSLP was mainly expressed by CD31-positive endothelial cells. In vitro, activated platelets induced TSLP production by HDMECs in an interleukin-1β-dependent manner. SSc fibroblasts responded differently according to their original TSLP environment.
  
  
  
  Taken together, these results identify HDMECs as contributors to TSLP production in SSc and suggest a potential mechanism by which platelets may profoundly affect the fibrotic process in SSc.
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Bordeaux Hospital, Bordeaux, France.
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Truchetet
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Demoures
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France, and Federal University of Alagoas, Maceió, Alagoas, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Eduardo Guimaraes
authors.affiliation: Bordeaux Hospital, Bordeaux, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bertrand
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.
authors.forename: Paôline
authors.initials: P
authors.lastname: Laurent
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Jolivel
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Douchet
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Jacquemin
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Khoryati
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Bordeaux Hospital, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duffau
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Bordeaux Hospital, Bordeaux, France.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Bordeaux Hospital, Bordeaux, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Richez
authors.affiliation: Bordeaux Hospital, Bordeaux, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Seneschal
authors.affiliation: Bordeaux Hospital, Bordeaux, France.
authors.forename: Marie-Sylvie
authors.initials: MS
authors.lastname: Doutre
authors.affiliation: Bordeaux Hospital, Bordeaux, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pellegrin
authors.affiliation: Bordeaux Hospital, Bordeaux, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Constans
authors.affiliation: Bordeaux Hospital, Bordeaux, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Schaeverbeke
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Bordeaux Hospital, Bordeaux, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blanco
authors.affiliation: CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Bordeaux Hospital, Bordeaux, France. cecile.bordes@chu-bordeaux.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Contin-Bordes
mesh_terms: D000328:Adult; D001792:Blood Platelets; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D020405:Dermis / Q000098:blood supply; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000166:cytology; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D045743:Scleroderma, Diffuse / Q000378:metabolism / Q000473:pathology; D045745:Scleroderma, Limited / Q000378:metabolism / Q000473:pathology; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000473:pathology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C508585:IL1B protein, human; D053583:Interleukin-1beta; D000094632:Thymic Stromal Lymphopoietin