[HTML][HTML] Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation

M Nakaya, Y Xiao, X Zhou, JH Chang, M Chang… - Immunity, 2014 - cell.com
M Nakaya, Y Xiao, X Zhou, JH Chang, M Chang, X Cheng, M Blonska, X Lin, SC Sun
Immunity, 2014cell.com
Glutamine has been implicated as an immunomodulatory nutrient, but how glutamine uptake
is mediated during T cell activation is poorly understood. We have shown that naive T cell
activation is coupled with rapid glutamine uptake, which depended on the amino acid
transporter ASCT2. ASCT2 deficiency impaired the induction of T helper 1 (Th1) and Th17
cells and attenuated inflammatory T cell responses in mouse models of immunity and
autoimmunity. Mechanistically, ASCT2 was required for T cell receptor (TCR)-stimulated …
Summary
Glutamine has been implicated as an immunomodulatory nutrient, but how glutamine uptake is mediated during T cell activation is poorly understood. We have shown that naive T cell activation is coupled with rapid glutamine uptake, which depended on the amino acid transporter ASCT2. ASCT2 deficiency impaired the induction of T helper 1 (Th1) and Th17 cells and attenuated inflammatory T cell responses in mouse models of immunity and autoimmunity. Mechanistically, ASCT2 was required for T cell receptor (TCR)-stimulated activation of the metabolic kinase mTORC1. We have further shown that TCR-stimulated glutamine uptake and mTORC1 activation also required a TCR signaling complex composed of the scaffold protein CARMA1, the adaptor molecule BCL10, and the paracaspase MALT1. This function was independent of IKK kinase, a major downstream target of the CARMA1 complex. These findings highlight a mechanism of T cell activation involving ASCT2-dependent integration of the TCR signal and a metabolic signaling pathway.
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