EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells
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. Mannan-induced psoriasis arthritis-like disease relies on the differentiation of MoDCs and Th17 cells. Reduced expression of EDIL3 was correlated with more severe symptoms in mannan-induced PsA. Additionally, EDIL3 knockout mice also exhibited more severe PsA disease, which could be reversed by reinfusion of recombinant EDIL3 protein. The alleviating effect of EDIL3 on PsA depends on the activation of MoDCs and Th17 cells. After neutralizing antibodies against MoDCs and Th17 cells were used to inhibit their function, the beneficial effect of EDIL3 on PsA was lost. Furthermore, EDIL3 can activate AMPK phosphorylation while reducing AKT phosphorylation, thereby slowing down mannose-induced intracellular glycolysis process in MoDCs and inhibiting their maturation and differentiation. Consequently, these compounds reduce the differentiation of Th17 cells and slow down the progression of PsA. Our results elucidate the role and mechanism through which EDIL3 contributes to the development of PsA, providing new targets for clinical diagnosis and treatment..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 28. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yu, Jiadong [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-3989780/v1 |
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| PPN (Katalog-ID): |
XRA042666376 |
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| 520 | |a 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. Mannan-induced psoriasis arthritis-like disease relies on the differentiation of MoDCs and Th17 cells. Reduced expression of EDIL3 was correlated with more severe symptoms in mannan-induced PsA. Additionally, EDIL3 knockout mice also exhibited more severe PsA disease, which could be reversed by reinfusion of recombinant EDIL3 protein. The alleviating effect of EDIL3 on PsA depends on the activation of MoDCs and Th17 cells. After neutralizing antibodies against MoDCs and Th17 cells were used to inhibit their function, the beneficial effect of EDIL3 on PsA was lost. Furthermore, EDIL3 can activate AMPK phosphorylation while reducing AKT phosphorylation, thereby slowing down mannose-induced intracellular glycolysis process in MoDCs and inhibiting their maturation and differentiation. Consequently, these compounds reduce the differentiation of Th17 cells and slow down the progression of PsA. Our results elucidate the role and mechanism through which EDIL3 contributes to the development of PsA, providing new targets for clinical diagnosis and treatment. | ||
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| 700 | 1 | |a Zhou, Yifan |4 aut | |
| 700 | 1 | |a Hu, Jing |4 aut | |
| 700 | 1 | |a Gu, Linna |4 aut | |
| 700 | 1 | |a Zhou, Hong |4 aut | |
| 700 | 1 | |a Yue, Chengcheng |4 aut | |
| 700 | 1 | |a Zhou, Pei |4 aut | |
| 700 | 1 | |a Li, Ya |4 aut | |
| 700 | 1 | |a Zhao, Qixiang |4 aut | |
| 700 | 1 | |a Zhang, Chen |4 aut | |
| 700 | 1 | |a Hu, Yawen |4 aut | |
| 700 | 1 | |a Zeng, Fanlian |4 aut | |
| 700 | 1 | |a Zhao, Fulei |4 aut | |
| 700 | 1 | |a Li, Guolin |4 aut | |
| 700 | 1 | |a Feng, Yuting |4 aut | |
| 700 | 1 | |a Wu, Wenling |4 aut | |
| 700 | 1 | |a Huang, Nongyu |4 aut | |
| 700 | 1 | |a Cui, Kaijun |4 aut | |
| 700 | 1 | |a Li, Jiong |4 aut | |
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