Background The role of IL17 cells in the pathogenesis of Systemic Sclerosis (SSc) has recently emerged, as it has been reported that IL-17 is overproduced by T cells from the peripheral blood and fibrotic lesions of the skin and lungs in SSc patients and it is able to enhance the proliferation of fibroblasts in vitro. In the latest years also the anti-inflammatory, anti-apoptotic, and anti-fibrotic effects of Vitamin D have gained considerable attention and it has been hypothesized that Vitamin D could have a modulating effect on SSc.
Objectives The aim of this study is to examine the in vitro expression of IL-17 and pro-fibrotic cytokines in peripheral blood mononuclear cells (PBMCs) from subjects with SSc and to evaluate the effects of IL-17 neutralizating antibodies and 25OH Vitamin D on the expression of these cytokines.
Methods PBMCs were isolated from 16 subjects fulfilling the 2013 ACR/EULAR criteria for SSc (16 women, mean age 51,3±6,7 years, range: 42-65); 10 matched healthy subjects (10 women, age 48,9±8,1 years, range: 41-61) was used as control. Secretion of IL-17 and pro-fibrotic cytokines (TGFβ, CTGF and PDGF) was detected by ELISA in PBMCs of both SSc and control group; the expression of specific mRNA for these cytokines was confirmed by RT-PCR analysis. To confirm the relationship between IL-17 and the expression of pro-fibrotic cytokines and to evaluate the possible anti-fibrotic effect of Vitamin D, the secretion and the expression of the pro-fibrotic cytokines were assessed in PBMCs from SSc after treatment with IL17 neutralizing antibodies or increasing concentrations (10-10 to 10-6 M) of 1,25(OH)2D3.
Results The expression of IL17, TGFβ, CTGF and PDGF was significantly higher in PBMCs from SSc subjects compared to healthy controls. Neutralization of IL-17 in the culture medium of SSc PBMCs decreased mRNA expression and protein secretion of TGFβ, CTGF and PDGF.
The addition of Vitamin D in SSc PBMCs significantly reduced the expression of pro-fibrotic cytokines compared to untreated cells only at higher concentration (10-6 M); with the same concentration of Vitamin D a slightly reduction of IL-17 production compared to untreated cells was observed, which did not reach statistical significance. Nevertheless, the inhibition of pro-fibrotic cytokines production induced by the higher concentration of Vitamin D was significantly lower compared to the inhibition induced by IL-17 neutralization.
Conclusions IL-17 is over-expressed in PBMCs of SSc subjects and is related to the higher expression of the pro.-fibrotic cytokines TGFβ, CTGF and PDGF. High concentrations of Vitamin D are able to partially inhibit the expression of these cytokines, supporting the hypothesis that supplementation of Vitamin D in SSc patients could have a potentially mitigating effect on fibrotic processes.
Yang X et al. Increased frequency of Th17 cells in systemic sclerosis is related to disease activity and collagen overproduction. Arthritis Res Ther. 2014 Jan 7;16(1):R4
Arnson Y et al. Amital H, Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev. 2011 Jun;10(8):490-4
Disclosure of Interest None declared