Journal
ISCIENCE
Volume 25, Issue 6, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.104435
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Funding
- Fondazione Cariplo [2015-0552, 2018-0511, 2019-1560]
- Telethon Foundation [GGP19146]
- European Foundation for the Study of Diabetes (EFSD)/Lilly European Diabetes Research Program
- Ministero dell'Universita`, Progetti di Rilevante Interesse Nazionale (PRIN) [PRIN 2017 K55HLC]
- Ministero della Salute, Ricerca Finalizzata [RF-2019-12370896]
- Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS)
- Televie
- Fondation Belge Contre le Cancer [FAF-F/2018/1282]
- European Research Council (ERC) independent researcher starting grant [243188]
- University of Milan
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This study investigated the impact of MCT1 deficiency on CD8(+) T cell function and found that MCT1 deficiency impaired CD8(+) T cell proliferation, shifted ATP production to mitochondrial oxidative phosphorylation, and affected the number of CD8(+) T cells infiltrating adipose tissue during obesity.
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 proliferationwith a shift of ATP production tomitochondrial oxidative phosphorylation. In Slc16a1(f/f )Tcell(cre) 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 togetherwith 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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