Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity

Summary: Lactate sits at the crossroad of metabolism, immunity, and inflammation. The expression of cellular lactate transporter MCT1 (known as Slc16a1) increases during immune cell activation to cope with the metabolic reprogramming. We investigated the impact of MCT1 deficiency on CD8+ T cell func...

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Main Authors: C. Macchi, A. Moregola, M.F. Greco, M. Svecla, F. Bonacina, S. Dhup, R.K. Dadhich, M. Audano, P. Sonveaux, C. Mauro, N. Mitro, M. Ruscica, G.D. Norata
Format: Article
Language:English
Published: Elsevier 2022-06-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222007064
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author C. Macchi
A. Moregola
M.F. Greco
M. Svecla
F. Bonacina
S. Dhup
R.K. Dadhich
M. Audano
P. Sonveaux
C. Mauro
N. Mitro
M. Ruscica
G.D. Norata
author_facet C. Macchi
A. Moregola
M.F. Greco
M. Svecla
F. Bonacina
S. Dhup
R.K. Dadhich
M. Audano
P. Sonveaux
C. Mauro
N. Mitro
M. Ruscica
G.D. Norata
author_sort C. Macchi
collection DOAJ
description Summary: Lactate sits at the crossroad of metabolism, immunity, and inflammation. The expression of cellular lactate transporter MCT1 (known as Slc16a1) increases during immune cell activation to cope with the metabolic reprogramming. We investigated the impact of MCT1 deficiency on CD8+ T cell function during obesity-related inflammatory conditions. The absence of MCT1 impaired CD8+ T cell proliferation with a shift of ATP production to mitochondrial oxidative phosphorylation. In Slc16a1f/fTcellcre mice fed a high-fat diet, a reduction in the number of CD8+ T cells, which infiltrated epididymal visceral adipose tissue (epiWAT) or subcutaneous adipose tissue, was observed. Adipose tissue weight and adipocyte area were significantly reduced together with downregulation of adipogenic genes only in the epiWAT. Our findings highlight a distinct effect of MCT1 deficiency in CD8+ T cells in the crosstalk with adipocytes and reinforce the concept that targeting immunometabolic reprogramming in lymphocyte could impact the immune-adipose tissue axis in obesity.
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spelling doaj.art-36f3cd08cf234da48a0992f6c1d01d1a2022-12-22T03:30:07ZengElsevieriScience2589-00422022-06-01256104435Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesityC. Macchi0A. Moregola1M.F. Greco2M. Svecla3F. Bonacina4S. Dhup5R.K. Dadhich6M. Audano7P. Sonveaux8C. Mauro9N. Mitro10M. Ruscica11G.D. Norata12Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyPole of Pharmacology, Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), Brussels, BelgiumPole of Pharmacology, Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), Brussels, BelgiumDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyPole of Pharmacology, Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), Brussels, BelgiumInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; Corresponding authorDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; SISA Center for the Study of Atherosclerosis, Bassini Hospital, Via M. Gorki 50, 20092 Milan, Cinisello Balsamo, Italy; Corresponding authorSummary: Lactate sits at the crossroad of metabolism, immunity, and inflammation. The expression of cellular lactate transporter MCT1 (known as Slc16a1) increases during immune cell activation to cope with the metabolic reprogramming. We investigated the impact of MCT1 deficiency on CD8+ T cell function during obesity-related inflammatory conditions. The absence of MCT1 impaired CD8+ T cell proliferation with a shift of ATP production to mitochondrial oxidative phosphorylation. In Slc16a1f/fTcellcre mice fed a high-fat diet, a reduction in the number of CD8+ T cells, which infiltrated epididymal visceral adipose tissue (epiWAT) or subcutaneous adipose tissue, was observed. Adipose tissue weight and adipocyte area were significantly reduced together with downregulation of adipogenic genes only in the epiWAT. Our findings highlight a distinct effect of MCT1 deficiency in CD8+ T cells in the crosstalk with adipocytes and reinforce the concept that targeting immunometabolic reprogramming in lymphocyte could impact the immune-adipose tissue axis in obesity.http://www.sciencedirect.com/science/article/pii/S2589004222007064Biological sciencesImmunologyMetabolomicsProteomics
spellingShingle C. Macchi
A. Moregola
M.F. Greco
M. Svecla
F. Bonacina
S. Dhup
R.K. Dadhich
M. Audano
P. Sonveaux
C. Mauro
N. Mitro
M. Ruscica
G.D. Norata
Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity
iScience
Biological sciences
Immunology
Metabolomics
Proteomics
title Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity
title_full Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity
title_fullStr Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity
title_full_unstemmed Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity
title_short Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity
title_sort monocarboxylate transporter 1 deficiency impacts cd8 t lymphocytes proliferation and recruitment to adipose tissue during obesity
topic Biological sciences
Immunology
Metabolomics
Proteomics
url http://www.sciencedirect.com/science/article/pii/S2589004222007064
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