EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells

• Published in: Inflammation 2024-09
• Main Authors: Yu, Jiadong, Wang, Xiaoyan, Zhou, Yifan, Hu, Jing, Gu, Linna, Zhou, Hong, Yue, Chengcheng, Zhou, Pei, Li, Ya, Zhao, Qixiang, Zhang, Chen, Hu, Yawen, Zeng, Fanlian, Zhao, Fulei, Li, Guolin, Feng, Yuting, He, Mingxiang, Huang, Shishi, Wu, Wenling, Huang, Nongyu, Cui, Kaijun, Li, Jiong
• Format: Article
• Language: English
• ISSN: 0360-3997; 1573-2576; 1573-2576
• DOI: 10.1007/s10753-024-02134-y

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.