Tissue-specific metabolic profile drives iNKT cell function during obesity and liver injury.

Autor:	Aguiar CF; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Corrêa-da-Silva F; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Gonzatti MB; Department of Microbiology, Immunology and Parasitology - Federal University of São Paulo, São Paulo, SP 04023-062, Brazil., Angelim MK; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Pretti MA; Bioinformatics and Computational Biology Lab, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20231-050, Brazil., Davanzo GG; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Castelucci BG; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Monteiro LB; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Castro G; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Virgilio-da-Silva JV; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Ribeiro G; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Jaccomo V; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Pereira Andrade MC; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Costa WL; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Gambarini V; School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand., Terra FF; Department of Immunology - Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil., Alves-Filho JC; Center for Research on Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil., Saraiva Câmara NO; Department of Immunology - Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil., Boroni M; Bioinformatics and Computational Biology Lab, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20231-050, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil., Keller AC; Department of Microbiology, Immunology and Parasitology - Federal University of São Paulo, São Paulo, SP 04023-062, Brazil., Moraes-Vieira PM; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil; Obesity and Comorbidities Research Center (OCRC), University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil. Electronic address: pmvieira@unicamp.br.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Jan 31; Vol. 42 (1), pp. 112035. Date of Electronic Publication: 2023 Jan 23.
DOI:	10.1016/j.celrep.2023.112035
Abstrakt:	Invariant natural killer T (iNKT) cells are a distinct population of lymphocytes characterized by their reactivity to glycolipids presented by CD1d. iNKT cells are found throughout the body, and little is known about their tissue-specific metabolic regulation. Here, we show that splenic and hepatic iNKT cells are metabolically comparable and rely on glycolytic metabolism to support their activation. Deletion of the pyruvate kinase M2 (Pkm2) gene in splenic and hepatic iNKT cells impairs their response to specific stimulation and their ability to mitigate acute liver injury. In contrast, adipose tissue (AT) iNKT cells exhibit a distinctive immunometabolic profile, with AMP-activated protein kinase (AMPK) being necessary for their function. AMPK deficiency impairs AT-iNKT physiology, blocking their capacity to maintain AT homeostasis and their ability to regulate AT inflammation during obesity. Our work deepens our understanding on the tissue-specific immunometabolic regulation of iNKT cells, which directly impacts the course of liver injury and obesity-induced inflammation. Competing Interests: Declaration of interests The authors declare that they have no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu