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Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway

Ipseiz, Natacha, Pickering, Robert J., Rosas, Marcela, Tyrrell, Victoria J., Davies, Luke C., Orr, Selinda J., Czubala, Magdalena A., Fathalla, Dina, Robertson, Avril A. B., Bryant, Clare E., O'Donnell, Valerie and Taylor, Philip R. 2020. Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway. EMBO Journal 39 (14) , e103454. 10.15252/embj.2019103454

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: EMBO Press
ISSN: 0261-4189
Funders: Wellcome Trust, MRC
Date of First Compliant Deposit: 10 June 2020
Date of Acceptance: 30 April 2020
Last Modified: 05 Jan 2022 03:57

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