Th17 peripheral cells are increased in diffuse cutaneous systemic sclerosis compared with limited illness: a cross-sectional study

Abstract

Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vasculopathy. A key feature is the presence of T cells in inflammatory lesions. To establish the differences in peripheral blood T helper (Th) subpopulations in diffuse cutaneous (dc) and limited cutaneous (lc) SSc patients, blood samples from 57 dcSSc and 78 lcSSc patients were obtained. Controls were collected from healthy volunteers (n = 16), active systemic lupus erythematosus (aSLE) patients (n = 13), and active rheumatoid arthritis (aRA) patients (n = 12). Mononuclear cells were analyzed by flow cytometry to determine Th1 (CD4+/IFN-γ+), Th2 (CD4+/IL-4+), Th17 (CD4+/IL-17+), and regulatory T cells (Tregs; CD4+/CD25+/Foxp3+) subsets. Th17 and Th1 subsets were increased in SSc groups versus healthy controls (P < 0.001) and aSLE patients (P < 0.001 for Th17 and P < 0.008 for Th1). Th2 cells were higher in dcSSc patients than in the healthy and aSLE groups (P = 0.03 and P = 0.009, respectively). Tregs were increased in the aRA group when compared with SSc patients and healthy controls (P ≤ 0.003). Patients with immunosuppressive treatment had lower numbers of Th17 and Th2 cells (P = 0.02). Our results shed further light into the preponderant role of Th17 and Th1 in patients with SSc. However, these findings certainly deserve to be studied in depth.

Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis

“…Our results confirmed earlier findings that Th17 responses predominate in active disease courses with elevated inflammatory blood parameters and diffuse manifestations of SSc [3,4,5,7,28]. Moreover, our findings demonstrated higher Th17-associated markers with lower chronological age or shorter disease duration, indicating an important role of Th17 in the early stages of the disease.…”

“…CCR6 expression was used as a characteristic marker of IL-17-producing cells [3,4,5,6,7,8] (Fig. 1A).…”

“…Increased expression of IL-17 mRNA by lymphocytes obtained from the skin and lung of SSc patients and elevated serum IL-17 levels suggest a role of IL-17 in the pathogenesis of SSc [3,6]. While some studies reported Th17 responses predominate in active disease courses and diffuse manifestations of scleroderma [7], others noted an absence of IL-17 production but a distinct T-cell subpopulation characterized by synthesis of IL-22, i.e. Th22 cells [8].…”

Environmental risk factors of systemic sclerosis

“…This Th17 response was characterized by high levels of IL-17 triggered or maintained by other cytokines (e.g., IL-6, IL-23, TGF-β) [44]. Interestingly, Th17 responses have been implicated in the pathogenesis of SSc [45,46].…”

The role of the acquired immune response in systemic sclerosis

“…While the frequency of Th17 lymphocytes is low in the peripheral blood of healthy individuals (~1 %), this subset undergoes recruitment and expansion in sites of active inflammation and tissue damage [4]. Increased levels of IL-17 and Th17 cells have been found in the peripheral blood as well as within target tissues (i.e., the skin) of SSc patients particularly during early phases and in association with ILD [27, 62,63,73,86,89,106,108,120]. In addition, cytokines crucial for Th17 T cell priming and expansion such as IL-6 and IL-23 have been reported enriched in SSc subjects, and a polymorphism of the IL-23 receptor gene (IL23R) has shown association with diffuse SSc and antitopoisomerase 1 positivity [1, 41, 50].…”