Premium
Platelets Induce Thymic Stromal Lymphopoietin Production by Endothelial Cells: Contribution to Fibrosis in Human Systemic Sclerosis
Author(s) -
Truchetet MarieElise,
Demoures Béatrice,
Eduardo Guimaraes Jorge,
Bertrand Anne,
Laurent Paôline,
Jolivel Valérie,
Douchet Isabelle,
Jacquemin Clément,
Khoryati Liliane,
Duffau Pierre,
Lazaro Estibaliz,
Richez Christophe,
Seneschal Julien,
Doutre MarieSylvie,
Pellegrin JeanLuc,
Constans Joël,
Schaeverbeke Thierry,
Blanco Patrick,
ContinBordes Cécile
Publication year - 2016
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39817
Subject(s) - thymic stromal lymphopoietin , cd31 , fibrosis , immunology , platelet , medicine , real time polymerase chain reaction , andrology , pathology , cytokine , immunohistochemistry , biology , biochemistry , gene
Objective 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. Methods 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. Results 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. Conclusion 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.