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

ABSTRACT: The alarm cytokine interleukin-1? (IL-1?) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1? production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1?; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL-1? from its pro-form. However, despite the important role of IL-1? 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? 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? processing, providing a previously unrecognized control of IL-1? in tissue-resident macrophages.

SUBMITTER: Ipseiz N 

PROVIDER: S-EPMC7360975 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature