Metabolic regulation of inflammation

Abstract

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

“…Immune cells sense environmental and metabolic cues that induce specialized stress responses in these cells (Chovatiya and Medzhitov, 2014). Flexibility of immune cells to adapt to different metabolic demands and diverse metabolic milieu via dynamic regulation of intracellular metabolism is an important component of inflammation and tissue homeostasis (Gaber et al, 2017). However, the underlying molecular mechanisms remain poorly understood.…”

Metabolic abnormalities and oxidative stress in lupus

“…The emerging field of immunometabolism has provided critical insights into the metabolic changes that immune cells undergo upon activation [1,2]. Reprogramming of immune cell metabolism is required to sustain the energy demands of effector functions such as differentiation, clonal expansion, secretion of proinflammatory mediators, phagocytosis, and tissue migration.…”

Biomaterial‐Based Metabolic Regulation in Regenerative Engineering

“…Anabolic glycolysis, PPP [8] Mesenchymal stem cells (MSCs) Low glycolysis [8,27,35] Endothelial cells Tip cells Increased aerobic glycolytic (stimulated by VEGF) [29,30] Stalk cells Aerobic glycolytic; fatty acid catabolism for nucleotide biosynthesis [29,30] Phalanx cells Low aerobic glycolysis [29,30] Immune cells Neutrophils Aerobic glycolysis; PPP [32,33] M1 macrophage Aerobic glycolysis; PPP [32,33,73] M2 macrophage Fatty acid oxidation [32,33,73] Activated dendritic cells (DCs) Aerobic glycolysis; PPP [32,33] Resting T cells Low glycolysis; low OXPHOS [32,33] Activated T cells Aerobic glycolysis [32,33] Regulatory T cells (T reg ) Fatty acid oxidation [32,33] Memory T cells Fatty acid oxidation [32,33] Differentiated cells Osteoblasts High OXPHOS; glutaminolysis [28,34] Adipocytes High OXPHOS; high ROS [28,34] Chondrocytes High glycolysis [28] Neurons High OXPHOS [38] Cardiomyocytes High OXPHOS; fatty acid oxidation [9] Myoblasts Anabolic glycolysis; PPP [28] Abbreviations: PPP, pentose phosphate pathway; VEGF, vascular endothelial grow factor; OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species.…”

“…[72] Moreover, ROS produced from immune cells (e.g., neutrophils and M1 macrophages) exhibiting antimicrobial effects represent ROS as a wellknown component in the host defense toward microbial invasion. [73] Therefore, cellular redox state has to be intricately regulated to maintain healthy cellular functions while preventing oxidative damage.…”