4.7 Article

Regulation of inflammasomes by autophagy

Journal

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 138, Issue 1, Pages 28-36

Publisher

MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.05.009

Keywords

Autophagy; host defense; inflammasome; inflammatory disorders; innate immunity; macrophages; organelle; pattern recognition receptors; reactive oxygen species; signal transduction

Funding

  1. Japan Society for the Promotion of Science KAKENHI [15H01380, 26111514, 26713005]
  2. Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology
  3. Japan Foundation for Pediatric Research
  4. LOTTE Foundation
  5. Takeda Science Foundation
  6. Mochida Memorial Foundation for Medical and Pharmaceutical Research
  7. Naito Foundation
  8. Tokyo Biochemical Research Foundation
  9. Grants-in-Aid for Scientific Research [15H01380, 26111514, 26713005, 15K14951] Funding Source: KAKEN

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Inflammasomes detect pathogen-associated molecular patterns to induce inflammatory innate immune responses and play a key role in host defense against infectious agents. However, inflammasomes are often wrongly activated by metabolites, amyloids, and environmental irritants. This induces massive inflammation, causing severe tissue damage, and results in the development of inflammatory diseases. Hence cellular machineries regulating both activation'' and inactivation'' of inflammasomes are definitely important. Recent studies have shown that autophagy, an intracellular degradation system associated with maintenance of cellular homeostasis, plays a key role in inflammasome inactivation. Notably, autophagy deficiency caused by gene mutation disrupts organelle elimination and thus induces aberrant activation of inflammasomes, leading to severe tissue damage. Here we review recent findings regarding the involvement of autophagy in the regulation of inflammasome activation and development of inflammatory disorders.

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