Lymphomonocytic Extracellular Vesicles Influence Fibroblast Proliferation and Collagen Production in Systemic...

Area of Science:

• Immunology
• Cell Biology
• Rheumatology

Background:

• Systemic sclerosis (SSc) is an autoimmune disease marked by fibrosis, immune issues, and vascular problems.
• Extracellular vesicles (EVs) from immune cells are involved in SSc by affecting fibroblast activity.
• Understanding EV influence on fibroblasts is key to SSc pathogenesis.

Purpose of the Study:

• To investigate how lymphomonocytic-derived EVs impact fibroblast proliferation and collagen synthesis in SSc.
• To compare the effects of EVs on healthy donor fibroblasts (HDFs) versus SSc patient fibroblasts (SScHDFs).

Main Methods:

• Fibroblasts (HDFs and SScHDFs) were treated with EVs from Jurkat and U937 cell lines.
• Immune cells were stimulated with pro-inflammatory agents: tumor necrosis factor-alpha (TNFα) or phorbol 12-myristate 13-acetate + ionomycin (PMA + IONO).
• Fibroblast proliferation was measured using CCK-8 assays, and collagen production was quantified via ELISA.

Main Results:

• EVs from PMA + IONO-stimulated immune cells dose-dependently reduced proliferation in both HDFs and SScHDFs.
• SScHDFs showed lower baseline proliferation and a weaker response to EV treatment.
• EVs from PMA + IONO-stimulated cells decreased collagen production in both fibroblast types.
• TNFα-stimulated EVs reduced collagen production only in HDFs.

Conclusions:

• Activated immune cell-derived EVs modulate fibroblast proliferation and collagen synthesis, impacting SSc.
• EVs may contribute to SSc pathogenesis by altering fibroblast function.
• Targeting EV-mediated signaling presents a potential therapeutic strategy for SSc.