T-Cell Proapoptotic and Antifibrotic Activity Against Autologous Skin Fibroblasts in vitro Is Associated With IL-17A Axis Upregulation in Systemic Sclerosis

• Published in: Frontiers in immunology 2020-02, Vol.11, p.220-220
• Main Authors: Vettori, Serena, Barra, Giusi, Russo, Barbara, Borgia, Alessia, Pasquale, Giuseppe, Pellecchia, Luciana, Vicedomini, Lucia, De Palma, Raffaele
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Blocking - metabolism; Apoptosis; Autoantigens - immunology; Cells, Cultured; co-cultures; Collagen Type I - metabolism; Female; fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Humans; IL-17A; Immunology; Interleukin-17 - metabolism; Male; Middle Aged; Receptors, Interleukin-17 - immunology; Scleroderma, Systemic - immunology; Signal Transduction; Skin - pathology; systemic sclerosis; T cells; Th17 Cells - immunology; Up-Regulation; Young Adult
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.00220

Systemic sclerosis (SSc) T cells can induce apoptosis of autologous skin fibroblasts . Th17 cells have been reported to increase in SSc patients, and interleukin-17A (IL-17A) has a profibrotic function. We used a system based on T-cell-autologous fibroblast co-cultures to further investigate a possible role of IL-17A in SSc. T cells from diffuse SSc patients were co-cultured with autologous skin fibroblasts. mRNA was assessed by real-time PCR in co-cultured and control T cells, while , and mRNAs were assessed in co-cultured and control fibroblasts. In subset experiments, co-cultures and control cells were treated with either IL-17A or IL-17A anti-IL17 receptor monoclonal antibody (α-IL-17RA mAb). Chemokine and procollagen type I (PCI) production was further investigated at the protein level in cell culture supernatants by multiple suspension immunoassay and sandwich ELISA, respectively. Co-cultured and control fibroblasts were also stained with Annexin V and analyzed by flow cytometry. T cell-fibroblast co-cultures overexpressed and . Furthermore, co-cultured fibroblasts upregulated IL-17A targets , and , while , and two key effectors of the TGF-β signaling, and , were found downregulated. Consistently, chemokine concentrations were increased in co-culture supernatants, while PCI levels were reduced, especially after stimulation with ectopic IL-17A. Finally, simultaneous α-IL-17RA mAb treatment restored PCI levels and reduced fibroblast apoptosis in IL-17A-stimulated co-cultures. These data suggest that IL-17A upregulation might play a role in modulating T cell-mediated antifibrotic and proapoptotic effects in co-cultured autologous skin fibroblasts.