Interleukin-36α is elevated in diffuse systemic sclerosis and may potentiate fibrosis

Area of Science:

• Immunology
• Dermatology
• Rheumatology

Background:

• Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular changes, inflammation, and skin fibrosis.
• The Interleukin-1 (IL-1) cytokine family is implicated in SSc pathogenesis.
• The specific role of IL-36α, an IL-1 family member known for its role in psoriasis, in SSc remains unclear.

Purpose of the Study:

• To investigate the levels of IL-36α in systemic sclerosis patients.
• To elucidate the functional role of IL-36α in SSc-associated skin pathology.

Main Methods:

• Serum samples from early diffuse SSc patients and healthy controls were analyzed for IL-36α levels using ELISA.
• Primary human dermal fibroblasts and keratinocytes were treated with recombinant IL-36α in vitro.
• Cytokine production (including CCL20 and CCL2) and signaling pathways (MAPK) were assessed.

Main Results:

• Serum IL-36α levels were significantly higher in SSc patients compared to healthy controls.
• Elevated neutrophil elastase was also observed in SSc patient sera.
• IL-36α did not directly induce fibrosis in dermal fibroblasts but stimulated pro-inflammatory cytokine release via the MAPK pathway.
• IL-36α induced CCL20 and CCL2 release from keratinocytes, suggesting a role in potentiating fibrosis.

Conclusions:

• IL-36α is elevated in the serum of patients with systemic sclerosis.
• IL-36α may contribute to SSc pathogenesis indirectly by promoting inflammation and potentially fibrosis through keratinocyte-immune cell crosstalk.
• Targeting IL-36α or its downstream effects could be a potential therapeutic strategy for SSc.