Targeting immunometabolism against acute lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions triggered by multiple intra- and extra-pulmonary injury factors, characterized by complicated molecular mechanisms and high mortality. Great strides have been made in the field of immunometabolism to clarify the interplay between intracellular metabolism and immune function in the past few years. Emerging evidence unveils the crucial roles of immunometabolism in inflammatory response and ALI. During ALI, both macrophages and lymphocytes undergo robust metabolic reprogramming and discrete epigenetic changes after activated. Apart from providing ATP and biosynthetic precursors, these metabolic cellular reactions and processes in lung also regulate inflammation and immunity.In fact, metabolic reprogramming involving glucose metabolism and fatty acidoxidation (FAO) acts as a double-edged sword in inflammatory response, which not only drives inflammasome activation but also elicits anti-inflammatory response. Additionally, the features and roles of metabolic reprogramming in different immune cells are not exactly the same. Here, we outline the evidence implicating how adverse factors shape immunometabolism in differentiation types of immune cells during ALI and summarize key proteins associated with energy expenditure and metabolic reprogramming. Finally, novel therapeutic targets in metabolic intermediates and enzymes together with current challenges in immunometabolism against ALI were discussed.

Automated summary

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions with complex molecular mechanisms and high mortality rates. In recent years, the field of immunometabolism has made significant progress in understanding the interaction between intracellular metabolism and immune function. Evidence has shown the important roles of immunometabolism in inflammatory response and ALI. Different immune cells undergo metabolic reprogramming and epigenetic changes during ALI, which not only provide energy and biosynthetic precursors, but also regulate inflammation and immunity. However, there are variations in the features and roles of metabolic reprogramming in different immune cells. This article outlines the impact of adverse factors on immunometabolism in different immune cell types during ALI, highlights key proteins associated with energy expenditure and metabolic reprogramming, and discusses potential therapeutic targets and challenges in immunometabolism against ALI.