Impaired Regulation by IL-35 in Systemic Sclerosis

Area of Science:

• Immunology
• Rheumatology
• Molecular Biology

Background:

• Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis and vascular abnormalities.
• The role of specific cytokines, such as Interleukin-35 (IL-35), in SSc pathogenesis remains incompletely understood.
• Understanding immune dysregulation in SSc is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To investigate the levels and function of IL-35 in patients with systemic sclerosis.
• To explore the relationship between IL-35, T cell responses, and disease severity markers in SSc.
• To evaluate the potential of IL-35 as a therapeutic target in SSc.

Main Methods:

• Enzyme-linked immunosorbent assays (ELISAs) were used to measure plasma IL-35, TGF-β, and IL-17 levels in SSc patients and healthy donors (HD).
• Flow cytometry was employed to assess IL-35 receptor (IL-35R) expression on various immune cell populations.
• Recombinant IL-35 (rIL-35) was added to stimulated peripheral blood mononuclear cells (PBMCs) and Treg:Tresponder co-culture assays to assess its immunomodulatory effects.

Main Results:

• SSc patients exhibited significantly lower plasma IL-35 concentrations compared to HDs (52.1 ± 5.6 vs. 143 ± 11.1, p < 0.001).
• IL-35 levels negatively correlated with TGF-β (p < 0.001) and IL-17 (p = 0.04) and positively with disease severity (mRSS, p = 0.004).
• rIL-35 suppressed IL-17A and TGF-β production and reduced T cell proliferation in vitro, demonstrating anti-inflammatory properties.

Conclusions:

• IL-35 plays a significant immunomodulatory role in systemic sclerosis.
• Reduced IL-35 levels in SSc patients are associated with increased pro-inflammatory cytokines and disease severity.
• IL-35 exhibits anti-inflammatory properties and represents a potential therapeutic target for SSc.