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Updated: Jun 12, 2025
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in
Jiadong Yu1, Xiaoyan Wang1, Yifan Zhou1,2
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Abstract:
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.
Insights
Epidermal growth factor-like repeats and discoidal domain-containing protein 1 (EDIL3) protein deficiency exacerbates psoriatic arthritis (PsA). Restoring EDIL3 ameliorates PsA by regulating immune cell differentiation and metabolism.
Area of Science:
- Immunology
- Biochemistry
- Rheumatology
Background:
- Psoriatic arthritis (PsA) is a chronic inflammatory joint disease linked to psoriasis.
- Epidermal growth factor-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with diverse physiological roles.
Purpose of the Study:
- To investigate the role and mechanism of EDIL3 in psoriatic arthritis (PsA) pathogenesis.
- To evaluate EDIL3 as a potential therapeutic target for PsA.
Main Methods:
- Utilized a mannan-induced psoriatic arthritis mouse model.
- Analyzed EDIL3 expression levels in PsA models.
- Investigated the effects of EDIL3 knockout and recombinant EDIL3 protein re-infusion.
- Examined the impact of EDIL3 on monocyte-derived dendritic cells (MoDCs) and T-helper 17 (Th17) cells.
- Assessed the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and protein kinase B (AKT) signaling pathways.
Main Results:
- EDIL3 expression was downregulated in the PsA model, correlating with disease severity.
- EDIL3 knockout mice showed exacerbated PsA phenotypes, which were improved by EDIL3 re-infusion.
- EDIL3 mitigated PsA by inhibiting MoDC and Th17 cell activation and differentiation.
- EDIL3 suppressed MoDC glycolysis via AMPK/AKT pathways, reducing inflammation and disease progression.
Conclusions:
- EDIL3 plays a protective role in psoriatic arthritis.
- EDIL3 regulates immune cell metabolism and differentiation, offering a novel therapeutic strategy for PsA.
- EDIL3 represents a potential biomarker and therapeutic target for psoriatic arthritis.
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