circIFNGR2 regulating ankylosing spondylitis-associated inflammation through macrophage polarization

Area of Science:

• Immunology
• Molecular Biology
• Rheumatology

Background:

• Macrophages play a key role in rheumatic diseases such as ankylosing spondylitis (AS).
• Circular RNAs (circRNAs) are implicated in autoimmune disease inflammation, but their role in AS is unclear.

Purpose of the Study:

• To investigate the role of circIFNGR2 in AS pathogenesis.
• To elucidate the molecular mechanisms by which circIFNGR2 influences macrophage activation and inflammation in AS.

Main Methods:

• Quantified circIFNGR2 expression in peripheral blood mononuclear cells from AS patients.
• Performed in vitro assays to assess circIFNGR2 effects on macrophage proliferation, polarization (M1/M2), and signaling pathways (NF-κB/Akt).
• Investigated the interaction between circIFNGR2, miR-939, and the RNA-binding protein eIF4A3.
• Evaluated the therapeutic potential of miR-939 and the effect of circIFNGR2 in a collagen-induced arthritis mouse model.

Main Results:

• circIFNGR2 expression was elevated in AS patients and correlated with disease severity.
• circIFNGR2 enhanced macrophage proliferation, promoted M1 polarization (via iNOS/TNFα), and suppressed M2 polarization by sponging miR-939.
• eIF4A3 was identified as a positive regulator of circIFNGR2 production.
• miR-939 demonstrated protective effects against joint damage in vivo, which were reversed by circIFNGR2.

Conclusions:

• eIF4A3-induced circIFNGR2 promotes AS pathogenesis by driving macrophage-associated inflammation via the miR-939 pathway.
• circIFNGR2 represents a potential therapeutic target for managing inflammation in ankylosing spondylitis.