Cell Reports (Jan 2023)
Tissue-specific metabolic profile drives iNKT cell function during obesity and liver injury
- Cristhiane Favero Aguiar,
- Felipe Corrêa-da-Silva,
- Michelangelo Bauwelz Gonzatti,
- Monara Kaelle Angelim,
- Marco Antonio Pretti,
- Gustavo Gastão Davanzo,
- Bianca Gazieri Castelucci,
- Lauar Brito Monteiro,
- Gisele Castro,
- João Victor Virgilio-da-Silva,
- Guilherme Ribeiro,
- Vitor Jaccomo,
- Mirella C. Pereira Andrade,
- Webster Leonardo Costa,
- Victor Gambarini,
- Fernanda Fernandes Terra,
- José Carlos Alves-Filho,
- Niels Olsen Saraiva Câmara,
- Mariana Boroni,
- Alexandre Castro Keller,
- Pedro M. Moraes-Vieira
Affiliations
- Cristhiane Favero Aguiar
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Felipe Corrêa-da-Silva
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Michelangelo Bauwelz Gonzatti
- Department of Microbiology, Immunology and Parasitology – Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
- Monara Kaelle Angelim
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Marco Antonio Pretti
- Bioinformatics and Computational Biology Lab, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20231-050, Brazil
- Gustavo Gastão Davanzo
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Bianca Gazieri Castelucci
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Lauar Brito Monteiro
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Gisele Castro
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- João Victor Virgilio-da-Silva
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Guilherme Ribeiro
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Vitor Jaccomo
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Mirella C. Pereira Andrade
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Webster Leonardo Costa
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology – Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil
- Victor Gambarini
- School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand
- Fernanda Fernandes Terra
- Department of Immunology – Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil
- José Carlos Alves-Filho
- Center for Research on Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School – University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil
- Niels Olsen Saraiva Câmara
- Department of Immunology – Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil
- Mariana Boroni
- 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
- Alexandre Castro Keller
- Department of Microbiology, Immunology and Parasitology – Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
- Pedro M. Moraes-Vieira
- 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; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 1
p. 112035
Abstract
Summary: 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.
