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- Title
Protectin DX restores Treg/T<sub>h</sub>17 cell balance in rheumatoid arthritis by inhibiting NLRP3 inflammasome via miR-20a.
- Authors
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
- Abstract
Regulatory T-cell (Treg)/T-helper 17 (Th17) 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/Th17 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 Th17 cells and pro-inflammatory cytokines. Moreover, NLRP3 knockout and rescue experiments demonstrated that NLRP3 participated in PDX-mediated Treg/Th17 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/Th17 cell balance, which was mediated by inhibition of the NLRP3 inflammasome pathway via miR-20a.
- Publication
Cell Death & Disease, 2021, Vol 12, Issue 3, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-021-03562-6