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Mitochondrial Pyruvate Carrier 1 Promotes Peripheral T Cell Homeostasis through Metabolic Regulation of Thymic Development.
- Source :
-
Cell reports [Cell Rep] 2020 Mar 03; Vol. 30 (9), pp. 2889-2899.e6. - Publication Year :
- 2020
-
Abstract
- Metabolic pathways regulate T cell development and function, but many remain understudied. Recently, the mitochondrial pyruvate carrier (MPC) was identified as the transporter that mediates pyruvate entry into mitochondria, promoting pyruvate oxidation. Here we find that deleting Mpc1, an obligate MPC subunit, in the hematopoietic system results in a specific reduction in peripheral αβ T cell numbers. MPC1-deficient T cells have defective thymic development at the β-selection, intermediate single positive (ISP)-to-double-positive (DP), and positive selection steps. We find that early thymocytes deficient in MPC1 display alterations to multiple pathways involved in T cell development. This results in preferred escape of more activated T cells. Finally, mice with hematopoietic deletion of Mpc1 are more susceptible to experimental autoimmune encephalomyelitis. Altogether, our study demonstrates that pyruvate oxidation by T cell precursors is necessary for optimal αβ T cell development and that its deficiency results in reduced but activated peripheral T cell populations.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Anion Transport Proteins deficiency
Gene Deletion
Glycolysis
Hematopoiesis
Humans
Inflammation pathology
Jurkat Cells
Lymphocyte Count
Mice
Mice, Inbred C57BL
Mitochondrial Membrane Transport Proteins deficiency
Monocarboxylic Acid Transporters deficiency
Oxidation-Reduction
Oxidative Phosphorylation
Pyruvic Acid metabolism
Thymocytes metabolism
Anion Transport Proteins metabolism
Homeostasis
Mitochondrial Membrane Transport Proteins metabolism
Monocarboxylic Acid Transporters metabolism
T-Lymphocytes metabolism
Thymus Gland growth & development
Thymus Gland metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 30
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 32130894
- Full Text :
- https://doi.org/10.1016/j.celrep.2020.02.042