Regulation of immune cell metabolism in health and disease: Special focus on T and B cell subsets.

Abstract

Metabolism is a dynamic process and keeps changing from time to time according to the demand of a particular cell to meet its bio-energetic requirement. Different immune cells rely on distinct metabolic programs which allow the cell to balance its requirements for energy, molecular biosynthesis, and effector activity. In the aspect of infection and cancer immunology, effector T and B cells get exhausted and help tumor cells to evade immunosurveillance. On the other hand, T cells become hyperresponsive in the scenario of autoimmune diseases. In this article, we have explored the uniqueness and distinct metabolic features of key CD4+ T and B helper cell subsets, CD4+ T, B regulatory cell subsets and CD8+ T cells regarding health and disease. Th1 cells rely on glycolysis and glutaminolysis; inhibition of these metabolic pathways promotes Th1 cells in Treg population. However, Th2 cells are also dependent on glycolysis but an abundance of lactate within TME shifts their metabolic dependency to fatty acid metabolism. Th17 cells depend on HIF-1α mediated glycolysis, ablation of HIF-1α reduces Th17 cells but enhance Treg population. In contrast to effector T cells which are largely dependent on glycolysis for their differentiation and function, Treg cells mainly rely on FAO for their function. Therefore, it is of utmost importance to understand the metabolic fates of immune cells and how it facilitates their differentiation and function for different disease models. Targeting metabolic pathways to restore the functionality of immune cells in diseased conditions can lead to potent therapeutic measures.