circIFNGR2 regulating ankylosing spondylitis-associated inflammation through macrophage polarization

Minkai Song  ¹ , Xiangyu Wang  ² , Jiawen Gao  ³ , Weizhou Jiang  ¹ , Enguang Bi  ⁴ , Taixue An  ⁵ , Ting Wang  ⁴ , Zishuo Chen  ⁴ , Weilu Liu  ¹ , Zhanjun Shi  ¹ , Jun Xiao  ¹ , Chao Zhang  ⁴

Affiliations

• PMID: 37520722
• PMCID: PMC10372825
• DOI: 10.1016/j.isci.2023.107325

Free PMC article

Abstract

Macrophages activation is crucial in pathogenesis of rheumatic diseases like ankylosing spondylitis (AS). Circular RNAs (circRNAs)-induced macrophage-associated inflammation participates in many autoimmune diseases but remains elusive in AS. Here, we verified increased expression of circIFNGR2 in peripheral blood mononuclear cells from patients with AS and its expression levels were correlated with the AS severity. In vitro assays revealed that circIFNGR2 enhances macrophage proliferation, and regulates M1/M2 macrophage polarization and NF-κB/Akt pathways. We identified that circIFNGR2 promoted the expression of iNOS/TNFα and M1 polarization, and restrained M2 polarization by sponging miR-939. Additionally, the RNA-binding protein, eIF4A3, was found to enhance the production of circIFNGR2. Interestingly, miR-939 attenuated joint damage in collagen-induced arthritis mice, whereas circIFNGR2 reversed this effect. Our findings highlight the pro-inflammatory roles of eIF4A3-induced circIFNGR2 in AS by modulating macrophage-associated inflammation through miR-939.

Keywords: Clinical genetics; Disease; Pathophysiology.