Utilize este identificador para referenciar este registo: https://hdl.handle.net/1822/44939

TítuloGlutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity
Autor(es)Arts, Rob J.W.
Novakovic, Boris
ter Horst, Rob
Carvalho, Agostinho Albérico Rodrigues
Bekkering, Siroon
Lachmandas, Ekta
Rodrigues, Fernando José dos Santos
Silvestre, Ricardo Jorge Leal
Cheng, Shih Chin
Wang, Shuang Yin
Gonçalves, Luís G.
Mesquita, Inês
Cunha, Cristina
van Laarhoven, Arjan
van de Veerdonk, Frank L.
Williams, David L.
van der Meer, Jos W.M.
Logie, Colin
O'Neill, Luke A.
Palavras-chaveEpigenetics
Glutamine metabolism
Cholesterol metabolism
Glycolysis
Trained immunity
DataDez-2016
EditoraElsevier
RevistaCell Metabolism
CitaçãoArts, R. J., Novakovic, B., ter Horst, R., Carvalho, A., et. al.(2016). Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metabolism, 24(6), 807-819
Resumo(s)Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by ß-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to ß-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by ß-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.
TipoArtigo
URIhttps://hdl.handle.net/1822/44939
DOI10.1016/j.cmet.2016.10.008
ISSN1550-4131
Versão da editorahttp://www.sciencedirect.com/science/article/pii/S1550413116305393
Arbitragem científicayes
AcessoAcesso aberto
Aparece nas coleções:ICVS - Artigos em revistas internacionais / Papers in international journals


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