Tissue-resident macrophages actively suppress IL-1beta release via a reactive prostanoid/IL-10 pathway
Open Access
- 14 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 39 (14), e103454
- https://doi.org/10.15252/embj.2019103454
Abstract
The alarm cytokine interleukin-1 beta (IL-1 beta) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1 beta production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1 beta; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL-1 beta from its pro-form. However, despite the important role of IL-1 beta in controlling local and systemic inflammation, its overall regulation is still not fully understood. Here we demonstrate that peritoneal tissue-resident macrophages use an active inhibitory pathway, to suppress IL-1 beta processing, which can otherwise occur in the absence of a second signal. Programming by the transcription factor Gata6 controls the expression of prostacyclin synthase, which is required for prostacyclin production after lipopolysaccharide stimulation and optimal induction of IL-10. In the absence of secondary signal, IL-10 potently inhibits IL-1 beta processing, providing a previously unrecognized control of IL-1 beta in tissue-resident macrophages.Keywords
Funding Information
- Wellcome Trust (099953/Z/12/Z)
- Medical Research Council (Dementia Research Institute)
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