Toggle Main Menu Toggle Search

Open Access padlockePrints

The Newcastle University research output collection, currently available on ePrints, will shortly be moving to a new open repository platform, Figshare. To prepare for the data migration we have paused adding new content to ePrints, and will resume once the new repository is launched. During this time you will continue to have access to ePrints (but no new content will appear). We will share updates here when available.

The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype

Lookup NU author(s): Dr Jodie Birch, Dr Joao Passos

Downloads

Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that, during oncogene-induced senescence (OIS), the Toll-like receptor 2 (TLR2) and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumor suppressors p53-p21CIP1, p16INK4a, and p15INK4b and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAAs) that, in turn, function as the damage-associated molecular patterns (DAMPs) signaling through TLR2 in OIS. Last, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAAs expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.

Publication metadata

Author(s): Hari P, Millar FR, Tarrats N, Birch J, Quintanilla A, Rink CJ, Fernandez-Duran I, Muir M, Finch AJ, Brunton VG, Passos JF, Morton JP, Boulter L, Acosta JC

Publication type: Article

Publication status: Published

Journal: Science Advances

Year: 2019

Volume: 5

Issue: 6

Print publication date: 05/06/2019

Acceptance date: 26/04/2019

Date deposited: 24/06/2019

ISSN (electronic): 2375-2548

Publisher: American Association for the Advancement of Science

URL: https://doi.org/10.1126/sciadv.aaw0254

DOI: 10.1126/sciadv.aaw0254

Altmetrics

Altmetrics provided by Altmetric

Share