Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling

Young Jun Kang (), Bo-Ram Bang, Kyung Ho Han, Lixin Hong, Eun-Jin Shim, Jianhui Ma, Richard A. Lerner and Motoyuki Otsuka
Additional contact information
Young Jun Kang: The Scripps Research Institute
Bo-Ram Bang: The Scripps Research Institute
Kyung Ho Han: The Scripps Research Institute
Lixin Hong: The Scripps Research Institute
Eun-Jin Shim: The Scripps Research Institute
Jianhui Ma: The Scripps Research Institute
Richard A. Lerner: The Scripps Research Institute
Motoyuki Otsuka: Graduate School of Medicine, University of Tokyo

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract The receptor-interacting protein kinase 3 (RIPK3) plays crucial roles in programmed necrosis and innate inflammatory responses. However, a little is known about the involvement of RIPK3 in NKT cell-mediated immune responses. Here, we demonstrate that RIPK3 plays an essential role in NKT cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5). RIPK3-mediated activation of PGAM5 promotes the expression of cytokines by facilitating nuclear translocation of NFAT and dephosphorylation of dynamin-related protein 1 (Drp1), a GTPase is essential for mitochondrial homoeostasis. Ripk3−/− mice show reduced NKT cell responses to metastatic tumour cells, and both deletion of RIPK3 and pharmacological inhibition of Drp1 protects mice from NKT cell-mediated induction of acute liver damage. Collectively, the results identify a crucial role for RIPK3-PGAM5-Drp1/NFAT signalling in NKT cell activation, and further suggest that RIPK3-PGAM5 signalling may mediate crosstalk between mitochondrial function and immune signalling.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9371 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:6:y:2015:i:1:d:10.1038_ncomms9371

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

DOI: 10.1038/ncomms9371

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 ().