Table 3 Genetic or pharmacological inhibition of amino acid transporters on immune cells and the functional consequences

T cells

SLC1A5

ASCT2

Asn

Genetic knockout in vitro

SLC1A5 is critical for uptake of Asn to promote CD8⁺ T cells activation

33,420,490

Gln

Chemical inhibition by V-9302 in vitro

V-9302 suppresses tumor progression but does not affect CD8⁺ T cells

29,334,372

Gln

Chemical inhibition by GPNA

Inhibition of SLC1A5 decreases TNF-α and IL-17 in PBMCs

30,541,099

SLC7A1^a

CAT1

Arg

Genetic knockout in vivo

Generation and persistence of memory T cells can be reprogrammed by SLC7A1 transporting Arg, partly via mTORC1

33,636,132

SLC7A5^a

LAT1

Met, Leu, Ile, Val, Phe, Trp

Genetic knockout in vitro

SLC7A5 is required for activated T cells to sustain Myc protein levels

32,022,686

Leu

Genetic knockout in vivo

TCR controls SLC7A5 expression is critical for metabolic reprogramming in T cells

23,525,088

Met

Genetic knockout in vivo

SLC7A5 null CD4⁺ T cells show a decrease of methyl donors

30,916,644

Kyn

Genetic knockout in vivo

Kyn transport in T cells is controlled and mediated through SLC7A5

29,773,791

SLC7A11^a

XCT

not mentioned

Genetic knockdown in vivo; Chemical inhibition by SAS in vitro;

Proliferation and function of Tregs was inhibited by depleting SLC7A11, but restored by DMF-induced upregulation of SLC7A11

34,004,141

SLC38A1

SNAT1

Gln

Genetic overexpression in vitro

Overexpression of SLC38A1 enhance mitochondrial function of CD4⁺ T cells

30,305,738

Ala

Genetic knockdown in vitro

Uptake of exogenous alanine by SLC38A1 is critical for primary CD4⁺ T cell mitogenesis

31,533,027

SLC38A2

SNAT2

Gln

Genetic knockout in vivo

Generation and persistence of memory T cells can be reprogrammed by SLC38A2 transporting Gln, partly via mTORC1

33,636,132

SLC43A2

LAT4

Met

Genetic knockdown in vitro

The downregulation of SLC43A2 increase apoptosis of Tregs due to the decrease in Met uptake

36,260,753

B cells

SLC7A5^a

LAT1

Leu

Expression stimulated by CpG ODN; blocked by BCH in vitro

Leu transport trough SLC7A5 is critical for B cell immune function

30,092,695

SLC15A4

His

Genetic knockout in vivo

SLC15A4 is required for B cell mTOR-dependent IFN-I response to TLR7 stimulation, contributing to lysosome environment optimization and autoantibody production

25,238,095

NK cells

SLC1A5, SLC7A5^a

ASCT2, LAT1

Gln

Targeted block by GPNA (SLC1A5) and D-phenylalanine (SLC7A5) in vitro

IL-2 priming increases SLC1A5 and SLC7A5 expression to promote IFN-γ production in NK cells

28,784,848

SLC3A2/SLC7A5^a

CD98/LAT1

Gln, Leu

Expression stimulated by IL-18 in vitro

IL-18 stimulates overexpression of SLC3a2/SLC7A5, inducing metabolic changes in NK cells

30,696,773

SLC7A5^a

LAT1

Gln, Leu

Genetic knockout in vivo

Leu is required for mTORC1 signaling and Gln is required to sustain cMyc expression when transported by SLC7A5 in NK cells

29,904,050

Macrophages

SLC1A2, SLC1A3

EAAT2, EAAT1

Glu

Competitively inhibited by D-Asp in vitro

Inhibition of SLC1A2 and SLC1A3 increase the glutamate-induced GSH in macrophages derived from monocytes

11,698,255

SLC7A2^a

CAT2

Arg

Genetic knockout in vivo

SLC7A2 KO reduces Arg uptake in macrophages, and impairs the catabolism of Arg

16,670,299

DCs

SLC3A2/SLC7A11^a

CD98/XCT

Glu, Cys

Targeted block by L-homocysteic acid in vivo

The block of SLC3A2/SLC7A11 heteromeric partners in DCs disrupts GSH homeostasis and may impair immunity in the diseased host

20,733,204

SLC15A4

His

Genetic knockout in vivo

SLC15A4 mutation leads to defective endosomal TLR signaling might due to compromised transport of His from endlysosome to cytosol in pDCs

35,349,343

His

Genetic knockout in vivo

SLC15A4-deficient DCs show reduced caspase-1 cleavage and IL-1β production by modulating mTORC1 function

36,031,853

MDSCs

SLC7A2^a

CAT2

Arg

Genetic knockout in vivo

Loss of SLC7A2 impairs the suppressive function of MDSCs in vitro, leads to increase in T cell numbers and decrease of tumor growth in vivo

26,491,198