Metabolite Transporters as Regulators of Immunity

Abstract

In the past decade, the rise of immunometabolism has fundamentally reshaped the face of immunology. As the functions and properties of many (immuno)metabolites have now been well described, their exchange among cells and their environment have only recently sparked the interest of immunologists. While many metabolites bind specific receptors to induce signaling cascades, some are actively exchanged between cells to communicate, or induce metabolic reprograming. In this review, we give an overview about how active metabolite transport impacts immune cell function and shapes immunological responses. We present some examples of how specific transporters feed into metabolic pathways and initiate intracellular signaling events in immune cells. In particular, we focus on the role of metabolite transporters in the activation and effector functions of T cells and macrophages, as prototype adaptive and innate immune cell populations.

Keywords: T cells; cell metabolism; immunity; macrophages; metabolite transporter; solute carrier.

Figure 1

Expression of metabolite transporters on T cells and their impact on T cell function. T cells express a variety of transporters to facilitate their metabolic needs. Import of fatty acids (FAs) of various sizes reduces inflammation through FA oxidation and IL-10 production, while import of lactate and acetate boosts inflammation. Transporters of the GLUT family take up glucose to increase glycolysis in activated T cells, while amino acid (AA) transport drives inflammation mainly via mTOR activation.

Figure 2

Expression of metabolite transporters on macrophages and their impact on macrophage function. As in T cells, glucose uptake is increased in pro-inflammatory macrophages, and AA uptake boosts mTOR activity. Cystine and glutamate, however, can limit mTOR activation through generation of cysteine and glutathione. Carnitine also exhibits anti-inflammatory potential, while FA uptake can limit glycolysis. Unlike in T cells, lactate uptake into macrophages is considered to be anti-inflammatory through inhibition of NF-κB.