Adefemi Folayemi, Fruman David A, Marshall Aaron J
Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, R3E-0T5 Winnipeg, Manitoba, Canada.
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; and.
J Immunol. 2020 Dec 15;205(12):3237-3245. doi: 10.4049/jimmunol.2000599.
PI3Ks activate critical signaling cascades and have multifaceted regulatory functions in the immune system. Loss-of-function and gain-of-function mutations in the PI3Kδ isoform have revealed that this enzyme can substantially impact immune responses to infectious agents and their products. Moreover, reports garnered from decades of infectious disease studies indicate that pharmacologic inhibition of the PI3K pathway could potentially be effective in limiting the growth of certain microbes via modulation of the immune system. In this review, we briefly highlight the development and applications of PI3K inhibitors and summarize data supporting the concept that PI3Kδ inhibitors initially developed for oncology have immune regulatory potential that could be exploited to improve the control of some infectious diseases. This repurposing of existing kinase inhibitors could lay the foundation for alternative infectious disease therapy using available therapeutic agents.
PI3K激活关键信号级联反应，在免疫系统中具有多方面的调节功能。PI3Kδ亚型的功能丧失和功能获得性突变表明，这种酶可对针对感染因子及其产物的免疫反应产生重大影响。此外，数十年来传染病研究获得的报告表明，PI3K通路的药理学抑制可能通过调节免疫系统有效限制某些微生物的生长。在本综述中，我们简要强调PI3K抑制剂的研发和应用，并总结支持以下概念的数据：最初为肿瘤学开发的PI3Kδ抑制剂具有免疫调节潜力，可用于改善对某些传染病的控制。现有激酶抑制剂的这种重新利用可为使用现有治疗药物的替代传染病疗法奠定基础。
