Metabolism in Immune Cell Differentiation and Function

Abstract

The immune system is a central determinant of organismal health. Functional immune responses require quiescent immune cells to rapidly grow, proliferate, and acquire effector functions when they sense infectious agents or other insults. Specialized metabolic programs are critical regulators of immune responses, and alterations in immune metabolism can cause immunological disorders. There has thus been growing interest in understanding how metabolic processes control immune cell functions under normal and pathophysiological conditions. In this chapter, we summarize how metabolic programs are tuned and what the physiological consequences of metabolic reprogramming are as they relate to immune cell homeostasis, differentiation, and function.

T cells and their immunometabolism: A novel way to understanding sepsis immunopathogenesis and future therapeutics

“…glutaminolysis) (Chapman et al, 2017;MacIver et al, 2013) (Fig.1). This glucose requirement is controlled by its uptake regulated by tonic TCR signaling that is defined as a low-level TCR signaling in response to self-peptide/MHC molecules and IL-7/IL-7receptor signaling required for the survival of naïve T cells (Chapman et al, 2017). Therefore absence of tonic TCR signaling may cause decreased GLUT1 (also known as SLC2A1) expression and decreased glucose uptake that may lead to the death of naïve T cells and their atrophy (Rathmell et al, 2000).…”

“…The immunometabolic stages and requirements of all the stages and types of T cells is discussed somewhere else in detail (Coe et al, 2014;Johnson et al, 2016;MacIver et al, 2013). The quiescent or naïve T cells are dependent on oxidative phosphorylation (OXPHOS) for their energy demand (Chapman et al, 2017). The pyruvic acid/pyruvate required for OXPHOS is obtained from glucose (i.e.…”

“…glycolysis), fatty acid oxidation (FAO) or amino acid metabolism (i.e. glutaminolysis) (Chapman et al, 2017;MacIver et al, 2013) (Fig.1). This glucose requirement is controlled by its uptake regulated by tonic TCR signaling that is defined as a low-level TCR signaling in response to self-peptide/MHC molecules and IL-7/IL-7receptor signaling required for the survival of naïve T cells (Chapman et al, 2017).…”

“…The mTORC1 has its six known protein components, while mTORC2 has seven components (Laplante and Sabatini, 2012). The proper balance between mTORC1 and mTORC2 signaling is also involved in immunometabolism of naïve T cells (Chapman et al, 2017;Chi, 2012;Yang and Chi, 2012). For example, lack of tuberous sclerosis complex 1 or TSC1 (a repressor of mTOR) causes an increased activity of mTORC1 signaling causing a metabolic dysfunction among naïve T cells and their apoptotic death (Chi, 2012;O'Brien et al, 2011;Wu et al, 2011).…”

Macrophage Function in the Pathogenesis of Non-alcoholic Fatty Liver Disease: The Mac Attack

“…Metabolic pathways regulate immune cell function and inflammation (81,82). Obesity alters cellular metabolism (83).…”