Sterols and immune mechanisms in asthma

The field of sterol and oxysterol biology in lung disease has recently gained attention, revealing a unique need for sterol uptake and metabolism in the lung. The presence of cholesterol transport, biosynthesis, and sterol/oxysterol-mediated signaling in immune cells suggests a role in immune regulation. In support of this idea, statin drugs that inhibit the cholesterol biosynthesis rate-limiting step enzyme, hydroxymethyl glutaryl coenzyme A reductase, show immunomodulatory activity in several models of inflammation. Studies in human asthma reveal contradicting results, whereas promising retrospective studies suggest benefits of statins in severe asthma. Here, we provide a timely review by discussing the role of sterols in immune responses in asthma, analytical tools to evaluate the role of sterols in disease, and potential mechanistic pathways and targets relevant to asthma. Our review reveals the importance of sterols in immune processes and highlights the need for further research to solve critical gaps in the field. (J Allergy Clin Immunol 2023;151:47-59.)

Automated summary

The role of sterols in immune responses in lung disease, particularly asthma, is discussed in this timely review. The presence of cholesterol transport, biosynthesis, and sterol/oxysterol-mediated signaling in immune cells suggests a role in immune regulation. Statin drugs, which inhibit cholesterol biosynthesis, show immunomodulatory activity in inflammation models, but conflicting results are seen in human asthma. Further research is needed to address critical gaps in the field.