Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction
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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.
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Autophagy inhibition increases free mtDNA in the cytosol and the production of IL-1β.
“Indeed, autophagy inhibition increases free mtDNA in the cytosol and the production of IL-1β (85).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [85]
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- Authors
- Shi, C.-S., Shenderov, K., Huang, N.-N., Kabat, J., Abu-Asab, M., Fitzgerald, K. A., Sher, A., & Kehrl, J. H.
- Affiliations
- National Institutes of Health (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Shi, Chong-Shan
- Kehrl, John H
- Venue
- Nature Immunology
- Published
- 2012-01-29
- Volume
- 13
- Issue
- 3
- Pages
- 255-263
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4116819
- OpenAlex
- W2042767581
- Cited by
- 1,367
- References
- 49
- Citations by year
- 2026: 36 · 2025: 72 · 2024: 70 · 2023: 99 · 2022: 121 · 2021: 98 · 2020: 122 · 2019: 92 · 2018: 98 · 2017: 102 · 2016: 123 · 2015: 96 · 2014: 89 · 2013: 100 · 2012: 48
- FWCI
- 42.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- Tokyo Medical and Dental University
- National Institutes of Health
- Takeda Oncology
- National Institute of Allergy and Infectious Diseases (Z01AI000739, R01AI083713)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- autophagy, inflammasome, IL-1β, AIM2 inflammasome, NLRP3 inflammasome, p62, ubiquitination, autophagosome formation, macrophages, caspase-1, inflammation regulation
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Autophagy, Carrier Proteins, Cell Line, DNA-Binding Proteins, Humans, Inflammation, Nuclear Proteins, Signal Transduction, ral GTP-Binding Proteins, Mice, Interleukin-1beta, Ubiquitination, Inflammasomes
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