Altered CD4+ T cell and cytokine levels in peripheral blood and skin samples from systemic sclerosis patients and IL35 in CD4+ T cell growth.

OBJECTIVE This study explored the role of IL-35 in CD4+ T lymphocyte and skin fibroblast (HSF) activity and cytokine levels in systemic sclerosis. METHODS Blood and skin biopsies were collected from 41 patients and 39 healthy controls to assess CD4+ T lymphocytes and IL-35-related factors. CD4+ T lymphocytes were co-cultured with HSFs, rhIL-35, and IL-35 mAb to evaluate the cell viability, activation of CD4+T lymphocytes, and HSF cells. RESULTS The proportion of blood Th1/Th2 was lower and Th17/regulatory T cells (Treg) were higher in patients than in controls (p < 0.05). IL-35 and IL-17A levels were higher and IFN-γ, IL-10, and TGF-β levels were lower in patients than in controls. IL-17A, FoxP3, TGF-β1, and COL-1 mRNA and p-STAT1 and p-STAT4 were higher in skin tissues from patients than in those from controls (p < 0.05). IL-6 levels were higher, whereas IL-10 levels were lower in cell culture supernatants. α-SMA and COL-1 proteins and Ki67 positivity were higher in CD4+ T + HSF cells from patients than in those from controls. rhIL-35 treatment inhibited proliferation (p < 0.001), but increased IL-10 and decreased IL-17A, α-SMA, and COL-1 secretion into the conditioned medium of CD4+ T lymphocytes + HSFs from patients compared with those from controls. IL-35 mAb blocked the effects of IL-35 in CD4+ T + HSF cells (p < 0.05). CONCLUSIONS IL-35 plays an inhibitory role in CD4+ T lymphocyte proliferation but induces Treg cell differentiation by STAT1 signalling activation, HSF proliferation, and collagen expression in systemic sclerosis.