The role of inflammasome-derived IL-1 in driving IL-17 responses

Our plain-English summary of The role of inflammasome-derived IL-1 in driving IL-17 responses, by K.H. Mills, L.S. Dungan, S.A. Jones, et al (Journal of Leukocyte Biology, 2013).

The study

• Authors: K.H. Mills, L.S. Dungan, S.A. Jones, J. Harris
• Journal: Journal of Leukocyte Biology
• Published: 2013;93(4):489-97
• Type of article: Review
• Cited by: 132 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

NLRs are members of the PRR family that sense microbial pathogens and mediate host innate immune responses to infection. Certain NLRs can assemble into a multiprotein complex called the inflammasome, which activates casapse-1 required for the cleavage of immature forms of IL-1β and IL-18 into active, mature cytokines. The inflammasome is activated by conserved, exogenous molecules from microbes and nonmicrobial molecules, such as asbestos, alum, or silica, as well as by endogenous danger signals, such as ATP, amyloid-β, and sodium urate crystals. Activation of the inflammasome is a critical event triggering IL-1-driven inflammation and is central to the pathology of autoinflammatory diseases, such as gout and MWS. Recent studies have also shown IL-1 or IL-18, in synergy with IL-23, can promote IL-17-prduction from Th17 cells and γδ T cells, and this process can be regulated by autophagy. IL-1-driven IL-17 production plays a critical role in host protective immunity to infection with fungi, bacteria, and certain viruses. However, Th17 cells and IL-17-seceting γδ T cells, activated by inflammasome-derived IL-1 or IL-18, have major pathogenic roles in many autoimmune diseases. Consequently, inflammasomes are now major drug targets for many autoimmune and chronic inflammatory diseases, as well as autoinflammatory diseases.

In plain English

This article is a review of published immunology research by authors at Trinity College Dublin. It did not study people exposed to asbestos. It described how a protein complex in immune cells, the inflammasome, activates an enzyme, caspase-1, which converts the signaling molecules IL-1β and IL-18 into their active forms. Asbestos was mentioned only in passing, with alum and silica, as a non-microbial substance that activates the inflammasome. The review summarized mainly mouse studies, some from the authors' own laboratory. These indicated that IL-1β and IL-18 act with IL-23 to drive immune cells that produce IL-17. It discussed this pathway's role in protection against certain infections, including Bordetella pertussis and Candida. It also discussed the pathway's links to autoimmune and inflammatory disease, including a mouse model of multiple sclerosis. It described how autophagy, a cellular recycling process, can limit IL-1β release and IL-23 secretion. The authors concluded that inflammasomes, caspase-1 and IL-1 are emerging as drug targets for autoimmune diseases. They added that blocking these pathways should be approached with caution because of their role in fighting infection.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published laboratory and clinical research on the inflammasome, IL-1 and IL-17
• Who was studied: No study population of its own. The review drew mainly on published mouse studies, with some evidence from human patients. The authors were at Trinity College Dublin, Ireland.
• Exposure: Asbestos was not studied. It was mentioned only as one of several non-microbial substances, with alum and silica, reported to activate the inflammasome. No fiber type was named.
• Main results:
  • In the review's account of studies from the authors' own laboratory using the mouse EAE model, inflammasome and caspase-1 activation in innate immune cells induced IL-1β and IL-18 production by dendritic cells. This in turn promoted Th17 cells.
  • The review described earlier work from the authors' laboratory showing that adenylate cyclase toxin from B. pertussis drove robust IL-1β production by dendritic cells.
  • The review cited a published study showing that caspase-1 and ASC protect against Candida through IL-1β and IL-18 production.
  • The review summarized published studies in which inducing autophagy limited IL-1β release.
  • The review also summarized published work in which inhibiting autophagy increased IL-23 secretion.
• The authors' conclusion: The authors concluded that inflammasomes, caspase-1 and IL-1 are emerging as drug targets for human autoimmune diseases. Because IL-1-driven Th17 cells help protect against fungal and bacterial infections, they cautioned that blocking these pathways should be approached with caution.

Topics

Medical terms in this study, explained in our Lexicon: Cytokine, Inflammation, Pathology.

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