Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.
Keywords: 3-PG, 3-phosphoglyceric acid; ABC, ATP-binding cassette; AIF, apoptosis-inducing factor; AP-1, activator protein 1; ASCT2, alanine serine and cysteine transporter system 2; ATP, adenosine triphosphate; BCR, B cell receptor; BMDMs, bone marrow-derived macrophages; CD45R, a receptor-type protein tyrosine phosphatase; CTL, cytotoxic T lymphocytes; DC, dendritic cells; EAATs, excitatory amino acid transporters; ER, endoplasmic reticulum; ERRα, estrogen related receptor alpha; FFA, free fatty acids; G-6-P, glucose 6-phosphate; GLUT, glucose transporters; GSH, glutathione; Glucose; Glutamine; HIF-1α, hypoxia-inducible factor 1-alpha; HIV-1, human immunodeficiency virus type 1; Hk1, hexokinase-1; IFNβ, interferon beta; IFNγ, interferon gamma; IKK, IκB kinase; IKKβ, IκB kinase beta subunit; IL, interleukin; LDHA, lactate dehydrogenase A; LPS, lipopolysaccharide; Lymphocytes; Lyn, tyrosine-protein kinase; MAPK, mitogen-activated protein kinase; MCT, monocarboxylate transporters; MS, multiple sclerosis; Metal ion; NADPH, nicotinamide adenine dinucleotide phosphate; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; NOD2, nucleotide-binding oligomerization domain containing 2; PEG2, prostaglandin E2; PI-3K/AKT, phosphatidylinositol-3-OH kinase/serine–threonine kinase; PPP, pentose phosphate pathway; Pfk, phosphofructokinase; RA, rheumatoid arthritis; RLR, RIG-I-like receptor; ROS, reactive oxygen species; SLC, solute carrier; SLE, systemic lupus erythematosus; SNAT, sodium-coupled neutral amino acid transporters; STAT, signal transducers and activators of transcription; Solute carrier; TAMs, tumor-associated macrophages; TCA, tricarboxylic acid; TCR, T cell receptor; TLR, toll-like receptor; TNF, tumor necrosis factor; TRPM7, transient receptor potential cation channel subfamily M member 7; Teffs, effector T cells; Th1/2/17, type 1/2/17 helper T cells; Tregs, regulatory T cells; VEGF, vascular endothelial growth factor; ZIP, zrt/irt-like proteins; iNOS, inducible nitric oxide synthase; iTregs, induced regulatory T cells; mTORC1, mammalian target of rapamycin complex 1; α-KG, α-ketoglutaric acid.
© 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.