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

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

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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


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