Conclusions
IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)2D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.
Methods
The production of IL-17A and pro-fibrotic cytokines (TGFβ, CTGF and FGF2) in PBMCs obtained from 51 SSc patients and 31 healthy subjects was assessed both in basal conditions and in presence of anti-IL17A antibodies and several concentrations of 1,25(OH)2D3. The association of cytokines production with clinical disease characteristics and the in vitro effect of 1,25(OH)2D3 and IL-17A inhibition were assessed.
Results
PBMCs from SSc subjects produced higher amount IL-17A, TGFβ, CTGF and FGF2 compared to healthy controls. IL17, TGFβ, CTGF and FGF2 levels were higher in SSc patients with interstitial lung disease and digital ulcers, whereas IL-17A production was lower in patients with PAH. IL- 17A inhibition reduced the production of FGF2, whereas enhanced the synthesis of TGFβ and CTGF. 1,25(OH)2D3 decreased the production of IL17A and pro-fibrotic cytokines in a dose- dependent manner. Conclusions: IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)2D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.