Optineurin modulates the maturation of dendritic cells to regulate autoimmunity through JAK2-STAT3 signaling

Jiajia Wang, Jiaying Wang, Wenxiang Hong, Lulu Zhang, Liqian Song, Qi Shi, Yanfei Shao, Guifeng Hao, Chunyan Fang, Yueping Qiu, Lijun Yang, Zhaoxu Yang, Jincheng Wang, Ji Cao, Bo Yang, Qiaojun He and Qinjie Weng ()
Additional contact information
Jiajia Wang: College of Pharmaceutical Sciences, Zhejiang University
Jiaying Wang: College of Pharmaceutical Sciences, Zhejiang University
Wenxiang Hong: College of Pharmaceutical Sciences, Zhejiang University
Lulu Zhang: College of Pharmaceutical Sciences, Zhejiang University
Liqian Song: College of Pharmaceutical Sciences, Zhejiang University
Qi Shi: College of Pharmaceutical Sciences, Zhejiang University
Yanfei Shao: People’s Hospital of Hangzhou Medical College
Guifeng Hao: People’s Hospital of Hangzhou Medical College
Chunyan Fang: College of Pharmaceutical Sciences, Zhejiang University
Yueping Qiu: College of Pharmaceutical Sciences, Zhejiang University
Lijun Yang: College of Pharmaceutical Sciences, Zhejiang University
Zhaoxu Yang: College of Pharmaceutical Sciences, Zhejiang University
Jincheng Wang: College of Pharmaceutical Sciences, Zhejiang University
Ji Cao: College of Pharmaceutical Sciences, Zhejiang University
Bo Yang: College of Pharmaceutical Sciences, Zhejiang University
Qiaojun He: College of Pharmaceutical Sciences, Zhejiang University
Qinjie Weng: College of Pharmaceutical Sciences, Zhejiang University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Optineurin (OPTN) has important functions in diverse biological processes and diseases, but its effect on dendritic cell (DC) differentiation and functionality remains elusive. Here we show that OPTN is upregulated in human and mouse DC maturation, and that deletion of Optn in mice via CD11c-Cre attenuates DC maturation and impairs the priming of CD4+ T cells, thus ameliorating autoimmune symptoms such as experimental autoimmune encephalomyelitis (EAE). Mechanistically, OPTN binds to the JH1 domain of JAK2 and inhibits JAK2 dimerization and phosphorylation, thereby preventing JAK2-STAT3 interaction and inhibiting STAT3 phosphorylation to suppress downstream transcription of IL-10. Without such a negative regulation, Optn-deficient DCs eventually induce an IL-10/JAK2/STAT3/IL-10 positive feedback loop to suppress DC maturation. Finally, the natural product, Saikosaponin D, is identified as an OPTN inhibitor, effectively inhibiting the immune-stimulatory function of DCs and the disease progression of EAE in mice. Our findings thus highlight a pivotal function of OPTN for the regulation of DC functions and autoimmune disorders.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26477-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26477-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26477-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().