No Cover Image

Journal article 67 views 3 downloads

Akt and STAT5 mediate naïve human CD4+ T-cell early metabolic response to TCR stimulation / Nicholas Jones; Emma E. Vincent; James G. Cronin; Silvia Panetti; Megan Chambers; Sean R. Holm; Sian E. Owens; Nigel J. Francis; David K. Finlay; Catherine A. Thornton

Nature Communications, Volume: 10, Issue: 1

Swansea University Author: Thornton, Catherine

  • 49646.pdf

    PDF | Version of Record

    Released under the terms of a Creative Commons Attribution 4.0 International license (CC-BY).

    Download (1.22MB)

Abstract

Metabolic pathways that regulate T-cell function show promise as therapeutic targets in diverse diseases. Here, we show that at rest cultured human effector memory and central memory CD4+ T-cells have elevated levels of glycolysis and oxidative phosphorylation (OXPHOS), in comparison to naïve T-cell...

Full description

Published in: Nature Communications
ISSN: 2041-1723
Published: 2019
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa49646
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract: Metabolic pathways that regulate T-cell function show promise as therapeutic targets in diverse diseases. Here, we show that at rest cultured human effector memory and central memory CD4+ T-cells have elevated levels of glycolysis and oxidative phosphorylation (OXPHOS), in comparison to naïve T-cells. Despite having low resting metabolic rates, naive T-cells respond to TCR stimulation with robust and rapid increases in glycolysis and OXPHOS. This early metabolic switch requires Akt activity to support increased rates of glycolysis and STAT5 activity for amino acid biosynthesis and TCA cycle anaplerosis. Importantly, both STAT5 inhibition and disruption of TCA cycle anaplerosis are associated with reduced IL-2 production, demonstrating the functional importance of this early metabolic program. Our results define STAT5 as a key node in modulating the early metabolic program following activation in naive CD4+ T-cells and in turn provide greater understanding of how cellular metabolism shapes T-cell responses.
Keywords: T cells, metabolism, glutamine, STAT5, TCA cycle
College: Swansea University Medical School
Issue: 1