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

Mako Nakaya, Yichuan Xiao, Xiaofei Zhou, Jae Hoon Chang, Mikyoung Chang, Xuhong Cheng, Marzenna Blonska, Xin Lin, Shao Cong Sun

Research output: Contribution to journalArticlepeer-review

349 Scopus citations

Abstract

Glutamine has been implicated as an immunomodulatory nutrient, but how glutamine uptake is mediated during Tcell activation is poorly understood. We have shown that naive Tcell 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 Tcell responses in mouse models of immunity and autoimmunity. Mechanistically, ASCT2 was required for Tcell 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 Tcell activation involving ASCT2-dependent integration of the TCR signal and a metabolic signaling pathway.

Original languageEnglish (US)
Pages (from-to)692-705
Number of pages14
JournalImmunity
Volume40
Issue number5
DOIs
StatePublished - May 15 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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