| First Author | Ipseiz N | Year | 2020 |
| Journal | EMBO J | Volume | 39 |
| Issue | 14 | Pages | e103454 |
| PubMed ID | 32484988 | Mgi Jnum | J:305706 |
| Mgi Id | MGI:6705291 | Doi | 10.15252/embj.2019103454 |
| Citation | Ipseiz N, et al. (2020) Tissue-resident macrophages actively suppress IL-1beta release via a reactive prostanoid/IL-10 pathway. EMBO J 39(14):e103454 |
| abstractText | The alarm cytokine interleukin-1beta (IL-1beta) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1beta production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1beta; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL-1beta from its pro-form. However, despite the important role of IL-1beta 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-1beta 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-1beta processing, providing a previously unrecognized control of IL-1beta in tissue-resident macrophages. |
