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A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging

Lanna, A; Gomes, DC; Muller-Durovic, B; McDonnell, T; Escors, D; Gilroy, DW; Lee, JH; ... Akbar, AN; + view all (2017) A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging. Nature Immunology , 18 (3) pp. 354-363. 10.1038/ni.3665. Green open access

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Abstract

Mitogen-activated protein kinases (MAPKs) including Erk, Jnk and p38 regulate diverse cellular functions and are thought to be controlled by independent upstream activation cascades. Here we show that the sestrins bind to and coordinate simultaneous Erk, Jnk and p38 MAPK activation in T lymphocytes within a new immune-inhibitory complex (sestrin-MAPK activation complex (sMAC)). Whereas sestrin ablation resulted in broad reconstitution of immune function in stressed T cells, inhibition of individual MAPKs allowed only partial functional recovery. T cells from old humans (>65 years old) or mice (16-20 months old) were more likely to form the sMAC, and disruption of this complex restored antigen-specific functional responses in these cells. Correspondingly, sestrin deficiency or simultaneous inhibition of all three MAPKs enhanced vaccine responsiveness in old mice. Thus, disruption of sMAC provides a foundation for rejuvenating immunity during aging.

Type: Article
Title: A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ni.3665
Publisher version: http://dx.doi.org/10.1038/ni.3665
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Adaptive immunity; Signal transduction
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1537644
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