Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Front Immunol. 2020 Nov 30;11:597945. doi: 10.3389/fimmu.2020.597945. eCollection 2020.
encodes an ER-resident transmembrane protein that regulates the activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme for sphingolipid biosynthesis in cells. A decade ago, several genome wide association studies revealed single nucleotide polymorphisms associated with increased ORMDL3 protein expression and susceptibility to allergic asthma. Since that time, numerous studies have investigated how altered ORMDL3 expression might predispose to asthma and other autoimmune/inflammatory diseases. In this brief review, we focus on growing evidence suggesting that heightened ORMDL3 expression specifically in CD4 T lymphocytes, the central orchestrators of adaptive immunity, constitutes a major underlying mechanism of asthma pathogenesis by skewing their differentiation and function. Furthermore, we explore how sphingolipid modulation in T cells might be responsible for these effects, and how further studies may interrogate this intriguing hypothesis.
编码一种内质网驻留跨膜蛋白，该蛋白调节丝氨酸棕榈酰转移酶（SPT）的活性，SPT 是细胞中鞘脂生物合成的第一限速酶。十年前，几项全基因组关联研究揭示了与 ORMDL3 蛋白表达增加和变应性哮喘易感性相关的单核苷酸多态性。从那时起，许多研究已经调查了改变 ORMDL3 表达如何可能导致哮喘和其他自身免疫/炎症性疾病。在这篇简短的综述中，我们重点介绍了越来越多的证据表明，适应性免疫的中枢协调者 CD4 T 淋巴细胞中 ORMDL3 表达的升高，通过使它们的分化和功能发生倾斜，构成了哮喘发病机制的主要潜在机制。此外，我们探讨了 T 细胞中鞘脂的调节如何可能导致这些影响，以及进一步的研究如何检验这一有趣的假设。
