Abstract
Recent findings show that the metabolic status of immune cells can determine immune responses. Metabolic reprogramming between aerobic glycolysis and oxidative phosphorylation, previously speculated as exclusively observable in cancer cells, exists in various types of immune and stromal cells in many different pathological conditions other than cancer. The microenvironments of cancer, obese adipose, and wound-repairing tissues share common features of inflammatory reactions. In addition, the metabolic changes in macrophages and T cells are now regarded as crucial for the functional plasticity of the immune cells and responsible for the progression and regression of many pathological processes, notably cancer. It is possible that metabolic changes in the microenvironment induced by other cellular components are responsible for the functional plasticity of immune cells. This review explores the molecular mechanisms responsible for metabolic reprogramming in macrophages and T cells and also provides a summary of recent updates with regard to the functional modulation of the immune cells by metabolic changes in the microenvironment, notably the tumor microenvironment.
Highlights
Pleiotropic interactions between various cells are responsible for the maintenance and disturbance of homeostasis in the tissue microenvironment of physiological and pathological conditions
A transcription factor, Myc, shows a dominant role in driving metabolic reprogramming in activated T cells by promoting glycolysis and glutaminolysis and suppressing fatty acid oxidation (FAO) [75]. mTOR increases expression of HIF-1α, which facilitates the expression of critical glycolytic enzymes and promotes differentiation and activation of T cells [76]
The lessons that application of immune checkpoint blockade antibodies against cytotoxic T lymphocyte antigen-4 (CTLA-4), PD-1, and PD-L1, which are used clinically, restore glucose in the tumor microenvironment (TME), permitting T cell glycolysis and IFNγ production clearly show that nutrient availability in the microenvironment can change the metabolic status of immune cells
Summary
Pleiotropic interactions between various cells are responsible for the maintenance and disturbance of homeostasis in the tissue microenvironment of physiological and pathological conditions. Lymphoid as well as myeloid cells infiltrates and expands in the liver tissue and the obese AT and these immune cell subsets are responsible for the development of obesityrelated metabolic dysregulation due to excessive nutrient intake and exacerbation of low-grade inflammatory changes in the microenvironment. Recent findings clearly show that the Warburg effect-like metabolic reprogramming exists in rapidly proliferating cells including various types of immune cells, most notably in macrophages and T cells, and determines the function of the immune cell subsets in disease conditions such as those in inflamed tissue or cancer [24,25,26,27]
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