Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction.

Abstract:

:Autophagosomes delivers cytoplasmic constituents to lysosomes for degradation, whereas inflammasomes are molecular platforms activated by infection or stress that regulate the activity of caspase-1 and the maturation of interleukin 1β (IL-1β) and IL-18. Here we show that the induction of AIM2 or NLRP3 inflammasomes in macrophages triggered activation of the G protein RalB and autophagosome formation. The induction of autophagy did not depend on the adaptor ASC or capase-1 but was dependent on the presence of the inflammasome sensor. Blocking autophagy potentiated inflammasome activity, whereas stimulating autophagy limited it. Assembled inflammasomes underwent ubiquitination and recruited the autophagic adaptor p62, which assisted their delivery to autophagosomes. Our data indicate that autophagy accompanies inflammasome activation to temper inflammation by eliminating active inflammasomes.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Shi CS,Shenderov K,Huang NN,Kabat J,Abu-Asab M,Fitzgerald KA,Sher A,Kehrl JH

doi

10.1038/ni.2215

subject

Has Abstract

pub_date

2012-01-29 00:00:00

pages

255-63

issue

3

eissn

1529-2908

issn

1529-2916

pii

ni.2215

journal_volume

13

pub_type

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