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. 2018 Jan 8;8:1889. doi: 10.3389/fimmu.2017.01889

Figure 1.

Figure 1

Regulatory T cells in tissue and blood compartments. The human liver is a hypoxic environment as the majority of blood flow is from the portal venous system. This leads to hypoxic induced factor 1-α (HIF-1α) activation, which subsequently enhances FoxP3 expression along with Th17 differentiation. Hypoxia leads to anaerobic glycolysis and extracellular lactic acid accumulation. Short-chain fatty acids (SCFAs) bind to the receptor GPCR43; long-chain fatty acids (LCFAs) bind to CD36, glutamine binds to ASCT2, and arginine binds to CAT2. Glucose transporter-1 (Glut-1) is poorly expressed on Treg cells compared with effector T cells. Liver Treg cells are mainly of an effector memory phenotype (RA−CCR7−). There is only minimal level of IL-2 present in the human liver compared with the blood, which restrict hepatic Treg function. Blood Treg-cell subsets are composed of effector memory (RA−CCR7−), central memory (RA−CCR7+), and naive (RA+CCR7+) phenotype. HIF-1α, Hypoxia-inducible factor 1α; HIF-1β, Hypoxia-inducible factor-1β; AhR, aryl hydrocarbon receptor; FA, Fatty acids; ARNT, Aryl Hydrocarbon Receptor Nuclear Translocator; mTOR, mammalian target of rapamycin; SCFA, short chain fatty acid; LCFA, long chain fatty acid; ASCT2, Alanine, serine, cysteine-preferring transporter 2; CAT, Cationic amino acid transporter; GPCR, G protein–coupled receptor.