The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation

• Published in: Cell metabolism Vol. 32; no. 3; pp. 468 - 478.e7
• Main Authors: Hooftman, Alexander, Angiari, Stefano, Hester, Svenja, Corcoran, Sarah E., Runtsch, Marah C., Ling, Chris, Ruzek, Melanie C., Slivka, Peter F., McGettrick, Anne F., Banahan, Kathy, Hughes, Mark M., Irvine, Alan D., Fischer, Roman, O’Neill, Luke A.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2020
• Subjects: Animals; cysteine modification; IL-1β; Immunologic Factors - pharmacology; immunometabolism; inflammasome; Inflammasomes - antagonists & inhibitors; Inflammasomes - metabolism; itaconate; macrophage; metabolite; Mice; Mice, Inbred C57BL; Mice, Knockout; NEK7; NLR Family, Pyrin Domain-Containing 3 Protein - deficiency; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; pyroptosis; Short; Succinates - pharmacology; pyroptosis; itaconate; metabolite; immunometabolism; inflammasome; NEK7; cysteine modification; NLRP3; macrophage; IL-1β

The Krebs cycle-derived metabolite itaconate is highly upregulated in inflammatory macrophages and exerts immunomodulatory effects through cysteine modifications on target proteins. The NLRP3 inflammasome, which cleaves IL-1β, IL-18, and gasdermin D, must be tightly regulated to avoid excessive infl...