Related Experiment Video

Updated: Mar 8, 2026

Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
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Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications

Published on: May 18, 2017

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

Alessio Lanna1,2, Daniel C O Gomes1,3, Bojana Muller-Durovic1

  • 1Division of Infection and Immunity, University College London, London, UK.

Nature Immunology
|January 24, 2017
PubMed

Insights

Sestrins form a complex that inhibits multiple mitogen-activated protein kinases (MAPKs) in T cells. Disrupting this complex rejuvenates immune function in aging, enhancing vaccine responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Mitogen-activated protein kinases (MAPKs), including Erk, Jnk, and p38, control crucial cellular functions.
  • MAPKs are typically regulated by distinct upstream signaling pathways.

Purpose of the Study:

  • To investigate the role of sestrins in coordinating MAPK activation in T lymphocytes.
  • To explore the potential of targeting the sestrin-MAPK complex for immune rejuvenation in aging.

Main Methods:

  • Identification and characterization of the sestrin-MAPK activation complex (sMAC).
  • Analysis of sestrin ablation and individual/simultaneous MAPK inhibition effects on T cell function.
  • Assessment of sMAC formation and function in T cells from young and aged humans and mice.
  • Evaluation of vaccine responsiveness in aged mice following sestrin deficiency or sMAC disruption.

Main Results:

  • Sestrins bind to and simultaneously activate Erk, Jnk, and p38 MAPKs within the novel sMAC.
  • Sestrin ablation broadly restored immune function in stressed T cells, unlike individual MAPK inhibition.
  • Aged T cells exhibited increased sMAC formation, which impaired antigen-specific responses.
  • Disrupting the sMAC or inhibiting all three MAPKs enhanced vaccine responsiveness in aged mice.

Conclusions:

  • The sestrin-MAPK activation complex (sMAC) represents a new immune-inhibitory mechanism in T cells.
  • Targeting the sMAC offers a potential strategy for rejuvenating age-related immune decline.
  • Disruption of the sMAC can restore immune function and improve vaccine efficacy in aged individuals.

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