Protectin DX restores Treg/T h 17 cell balance in rheumatoid arthritis by inhibiting NLRP3 inflammasome via miR-20a

Regulatory T-cell (Treg)/T-helper 17 (T 17) cell balance plays an important role in the progression of rheumatoid arthritis (RA). Our study explored the protective effect of protectin DX (PDX), which restored Treg/T 17 cell balance in RA, and the role of the nucleotide-binding domain (NOD)-like rece...

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Veröffentlicht in:Cell death & disease 2021-03, Vol.12 (3), p.280
Hauptverfasser: Jin, Shengwei, Sun, Siyuan, Ling, Hanzhi, Ma, Jinglan, Zhang, Xu, Xie, Zhen, Zhan, Ning, Zheng, Wenjie, Li, Man, Qin, Yang, Zhao, Heping, Chen, Yan, Yang, Xinyu, Wang, Jianguang
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Sprache:eng
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Zusammenfassung:Regulatory T-cell (Treg)/T-helper 17 (T 17) cell balance plays an important role in the progression of rheumatoid arthritis (RA). Our study explored the protective effect of protectin DX (PDX), which restored Treg/T 17 cell balance in RA, and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome pathway in this process. Using mass spectrometry, we discovered that level of PDX decreased in active-RA patients and increased in inactive-RA patients compared with HCs, and serum PDX was a potential biomarker in RA activity detection (area under the curve [AUC] = 0.86). In addition, a collagen-induced arthritis (CIA) mice model was constructed and PDX obviously delayed RA progression in the CIA model, upregulating Tregs and anti-inflammatory cytokines while downregulating T 17 cells and pro-inflammatory cytokines. Moreover, NLRP3 knockout and rescue experiments demonstrated that NLRP3 participated in PDX-mediated Treg/T 17 cell balance restoration, joint injury amelioration and inflammatory-response attenuation using Nlrp3 mice. Furthermore, microarray and verified experiments confirmed that PDX reduced NLRP3 expression via miRNA-20a (miR-20a). In summary, we confirmed for the first time that PDX could effectively ameliorate CIA progression by restoring Treg/T 17 cell balance, which was mediated by inhibition of the NLRP3 inflammasome pathway via miR-20a.
ISSN:2041-4889