Open AccessAmino-acid transporters in T-cell activation and differentiation
Author(s) -
Wenkai Ren,
Gang Liu,
Jie Yin,
Bin Tan,
Guoyao Wu,
Fuller W. Bazer,
Yuanyi Peng,
Yulong Yin
Publication year - 2017
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/cddis.2016.222
Subject(s) - transporter , amino acid transporter , mtorc1 , immune system , glutamine , biology , microbiology and biotechnology , t cell , amino acid , cellular differentiation , cell , biochemistry , chemistry , signal transduction , immunology , pi3k/akt/mtor pathway , gene
T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yielded surprising findings in the importance of amino-acid transporters for T-cell development, homeostasis, activation, differentiation and memory. In this review, we present current information on amino-acid transporters, such as LAT1 ( l -leucine transporter), ASCT2 ( l -glutamine transporter) and GAT-1 ( γ -aminobutyric acid transporter-1), which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells. Mechanically, the influence of amino-acid transporters on T-cell fate decision may largely depend on the mechanistic target of rapamycin complex 1 (mTORC1) signaling. These discoveries remarkably demonstrate the role of amino-acid transporters in T-cell fate determination, and strongly indicate that manipulation of the amino-acid transporter-mTORC1 axis could ameliorate many inflammatory or autoimmune diseases associated with T-cell-based immune responses.