Abstract
IntroductionAlthough immune dysfunction plays a role in the pathogenesis of systemic sclerosis (SSc), involvement of T helper 17 (Th17) and T regulatory (Treg) cells remains unclear. We aimed to investigate the presence of Th17 and Treg cells in SSc patients and the role of Th17 cells in collagen production in SSc fibroblasts.MethodsWe analyzed inflammatory cell profiles in the skin of 13 SSc patients by immunohistochemistry, the percentage of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) of 45 SSc patients and 24 healthy controls by flow cytometry, gene expression in PBMCs by real-time reverse transcription-polymerase chain reaction and interleukin-17 (IL-17) in sera and culture supernatants by enzyme-linked immunosorbent assay. We also investigated the effect of Th17 cell-derived IL-17 on fibroblast growth and collagen production.ResultsInfiltration of inflammatory cells including IL-17+ and Foxp3+ lymphocytes was detected in the skin of patients with early SSc. The percentages of circulating Th17 cells and IL-17 production were elevated in samples from patients with active SSc, whereas the percentage of circulating Treg cells was not affected. The number of Th17 cells was closely related to disease activity. IL-17 from SSc patients promoted fibroblast growth and collagen production, whereas IL-17 neutralizing antibody effectively blocked collagen production.ConclusionSSc progression might be linked to expansion of circulating Th17 cells and increased infiltration of IL-17+ cells in skin. Th17-derived IL-17 is involved in fibroblast growth and collagen production. IL-17 blocking antibody may be a useful tool for intervention in the fibrotic course of SSc.
Highlights
Immune dysfunction plays a role in the pathogenesis of systemic sclerosis (SSc), involvement of T helper 17 (Th17) and T regulatory (Treg) cells remains unclear
The percentage of Th17 cells is expanded in SSc patients, but the percentage of Treg cells is not significantly affected To investigate further these lymphocyte subgroups in peripheral blood mononuclear cells (PBMCs) of SSc patients, we studied 45 patients with SSc, including 13 patients with active SSc and 32 with stable SSc
Several lines of evidence suggest that T cells are important in the pathogenesis of SSc: first, T cells infiltrate skin early, before any evidence of fibrosis; second, an increased number of activated T cells is found in blood and skin lesions; third, T cells producing cytokines can induce fibroblast collagen production; fourth, T cells are necessary for antibody production; and fifth, treatments directed against T cells ameliorate systemic sclerosis [3]
Summary
Immune dysfunction plays a role in the pathogenesis of systemic sclerosis (SSc), involvement of T helper 17 (Th17) and T regulatory (Treg) cells remains unclear. We aimed to investigate the presence of Th17 and Treg cells in SSc patients and the role of Th17 cells in collagen production in SSc fibroblasts. Growing evidence suggests that T-cell proliferation and cytokine secretion play a major role in the pathogenesis of SSc [2,3,4], suggesting that this condition could be associated with a general defect in the control of T-cell activation [3]. We hypothesized that altered cytokine profiles in SSc patients might result in an imbalance of Th17/Treg cells, and might be responsible for the prominent features of SSc, such as fibroblast proliferation and endothelium injury [2,17]
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