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Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
Natacha Ipseiz, Robert J Pickering , Marcela Rosas, Victoria J Tyrrell, Luke Davies , Selinda J Orr, Magdalena A Czubala, Dina Fathalla, Avril AB Robertson, Clare E Bryant , Valerie O'Donnell, Philip R Taylor
The EMBO Journal, Volume: 39, Issue: 14
Swansea University Author: Luke Davies
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Copyright: 2020 The Authors. Published under the terms of the CC BY 4.0 licenseDownload (1.2MB)
DOI (Published version): 10.15252/embj.2019103454
The alarm cytokine interleukin-1β (IL-1β) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1β production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1β; subseque...
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The alarm cytokine interleukin-1β (IL-1β) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1β production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1β; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL-1β from its pro-form. However, despite the important role of IL-1β 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-1β 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-1β processing, providing a previously unrecognized control of IL-1β in tissue-resident macrophages.
s IL-10; IL-1beta; macrophages; prostacyclin
Faculty of Medicine, Health and Life Sciences
Wellcome Trust (WT). Grant Numbers: 107964/Z/15/Z, 103973/Z/14/Z, 108045/Z/15/Z;
Wellcome Trust and the Royal Society. Grant Number: 099953/Z/12/Z;
UK Research and Innovation|Medical Research Council (MRC). Grant Number: Dementia Research Institute