Immune cell metabolism and metabolic reprogramming

Abstract

Energy metabolism maintains the activation of intracellular and intercellular signal transduction, and plays a crucial role in immune response. Under environmental stimulation, immune cells change from resting to activation and trigger metabolic reprogramming. The immune system cells exhibit different metabolic characteristics when performing functions. The study of immune metabolism provides new insights into the function of immune cells, including how they differentiate, migrate and exert immune responses. Studies of immune cell energy metabolism are beginning to shed light on the metabolic mechanism of disease progression and reveal new ways to target inflammatory diseases such as autoimmune diseases, chronic viral infections, and cancer. Here, we discussed the relationship between immune cells and metabolism, and proposed the possibility of targeted metabolic process for disease treatment.

Keywords: Immune cells; Immune metabolism; Metabolic reprogramming; Targeted therapy.

Fig. 1

Simplified representation of glucose metabolic pathways. A Glycolysis occurs in the cytoplasm, converting glucose into pyruvate and then into lactic acid in the mitochondria. Under aerobic conditions, pyruvic acid is oxidized and decarboxylated to form acetyl CoA, which can be completely oxidized into TCA. Intermediates in glucose metabolism can flow to other metabolic pathways, such as PPP and FAS. B ETC refers to the structure of NADH or FADH2 transferring electrons to oxygen. OXPHOS causes the gain and loss of electrons on the electron carrier, which is transferred between redox substrates to form ETC

Fig. 2

Major metabolic patterns in macrophages. The metabolic modes of M1 and M2 are different. In M1, the increase of glucose uptake is used for glycolysis and PPP. While in M2, the main metabolic characteristics are the increase of FAO and OXPHOS. M1 induced by LPS/INF-γ are regulated by HIF1α. In LPS (+ IFN-γ)-activated inflammatory macrophages, HIF1α not only promotes glycolysis, but also induces the expression of genes encoding inflammatory cytokines, especially IL-1β and IL-6. In IL-4-induced macrophages, PPARγ as the main regulator can use the transported glucose for TCA cycle. FAO can promote the development and activity of anti-inflammatory macrophages. Moreover, FAO has been proved to support mitochondrial oxidation and metabolism of M2, and ATP is continuously through OXPHOS. In M2, the anti-inflammatory effect was exerted by activating the expression of anti-inflammatory genes such as CD36 and Argl

Fig. 3

The metabolic differences of Teffs, Tm, Tregs. When Tn cells were stimulated to recognize antigens, the resting state of energy supply by OHPHOS was broken. With the assistance of HIF1α and C-Myc, glutamine decomposition was enhanced, and a large amount of energy was provided by glycolysis. It will undergo a development process characterized by rapid growth, proliferation and acquisition of special effects, and then differentiate into Teffs, Tregs and Tm cells. FAO plays an important role in regulating T cell response. So far, FAO has been observed to regulate the balance between inflammatory Teffs and inhibitory Tregs, and maintain the function of long-lived Tm cells. Compared with Teffs, Tregs and Tm cells showed more FAO and OXPHOS, and FAO promoted the generation of Tregs. Interestingly, the down-regulation of FAO by Teffs depends more on glycolysis and TCA cycle energy supply. FOXP3 and AMPK promote the OXPHOS and increase ATP production to meet the energy supply in Tm cells and Tregs. mTOR increases glucose uptake by targeting Glut1, making Teffs play an effective role in the body