Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus.
Department of Pediatrics, The Ohio State University, Columbus.
J Allergy Clin Immunol. 2023 Jan;151(1):47-59. doi: 10.1016/j.jaci.2022.09.025. Epub 2022 Oct 29.
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.
固醇和氧化固醇生物学在肺部疾病领域的研究最近引起了关注,揭示了肺部对固醇摄取和代谢的独特需求。胆固醇转运、生物合成以及固醇/氧化固醇介导的信号在免疫细胞中的存在表明其在免疫调节中发挥作用。支持这一观点的是,抑制胆固醇生物合成限速酶羟甲基戊二酰辅酶 A 还原酶的他汀类药物在几种炎症模型中显示出免疫调节活性。人类哮喘的研究结果相互矛盾,而有前景的回顾性研究表明他汀类药物对严重哮喘有益。在这里,我们通过讨论固醇在哮喘免疫反应中的作用、评估固醇在疾病中作用的分析工具以及与哮喘相关的潜在机制途径和靶点,提供了一个及时的综述。我们的综述揭示了固醇在免疫过程中的重要性,并强调需要进一步研究来解决该领域的关键空白。