Nov 9, 2018

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

BioRxiv : the Preprint Server for Biology
Priya HariJuan Carlos Acosta

Abstract

Cellular senescence is a stress response program characterised by a robust cell cycle arrest and the induction of a pro-inflammatory 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 TLR2 and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumour suppressors p53-p21CIP1, p16INK4a and p15INK4b, and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAA) that, in turn, function as the damage associated molecular patterns (DAMPs) signalling through TLR2 in OIS. Finally, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAA 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.

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Mentioned in this Paper

Oncogene-induced Senescence
Biochemical Pathway
Biological Adaptation to Stress
Patterns
Cell Aging
TLR10 gene
Cdkn1a
TMEM173 gene
Cyclin-Dependent Kinase Inhibitor p16
Murine

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