Homeostatic and pathogenic roles of PI3Kδ in the human immune system.

3区 医学 Q2 Medicine
Advances in Immunology Pub Date : 2020-01-01 Epub Date: 2020-03-19 DOI:10.1016/bs.ai.2020.02.001
Georgios Sogkas, Ignatius Ryan Adriawan, Natalia Dubrowinskaja, Faranaz Atschekzei, Reinhold Ernst Schmidt
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引用次数: 10

Abstract

Phosphoinositide 3-kinase delta (PI3Kδ) mediates signaling transduction downstream of diverse immune receptors, including the T cell receptor (TCR), the B cell receptor (BCR), costimulatory molecules and cytokine receptors. Our understanding of the role of PI3Kδ in the immune system comes primarily from mice, and especially from the consequences of pharmacological inhibition of PI3Kδ in mouse models of human disease as well as the consequences of genetic manipulation, resulting in hyperactivation or loss of PI3Kδ function. In case of humans, in vitro studies with PI3Kδ-specific inhibitors, the consequences of treatment of hematologic malignancies with the PI3Kδ-specific inhibitor idelalisib and primary immunodeficiency disorders due to germline variants hyper- or underactivating PI3Kδ provide most of our knowledge on the role of PI3Kδ in immunity and immune regulation. In this review, we summarize the physiological and pathophysiological roles of PI3Kδ in the human immune system, focusing on immunodeficiency due to defects in PI3Kδ signaling and especially on the recently reported cases with mutations resulting in loss of PI3Kδ activity.

PI3Kδ在人体免疫系统中的稳态和致病作用。
磷酸肌肽3-激酶δ (PI3Kδ)介导多种免疫受体的下游信号转导,包括T细胞受体(TCR)、B细胞受体(BCR)、共刺激分子和细胞因子受体。我们对PI3Kδ在免疫系统中的作用的了解主要来自小鼠,特别是来自人类疾病小鼠模型中PI3Kδ的药理抑制的后果以及遗传操作的后果,导致PI3Kδ功能的过度激活或丧失。就人类而言,PI3Kδ特异性抑制剂的体外研究,PI3Kδ特异性抑制剂idelalisib治疗血液病恶性肿瘤的后果,以及由于种系变异导致的PI3Kδ高激活或低激活的原发性免疫缺陷疾病,提供了我们关于PI3Kδ在免疫和免疫调节中的作用的大部分知识。在这篇综述中,我们总结了PI3Kδ在人类免疫系统中的生理和病理生理作用,重点是由于PI3Kδ信号缺陷引起的免疫缺陷,特别是最近报道的突变导致PI3Kδ活性丧失的病例。
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来源期刊
Advances in Immunology
Advances in Immunology 医学-免疫学
CiteScore
9.90
自引率
0.00%
发文量
13
期刊介绍: Advances in Immunology has provided students and researchers with the latest information in Immunology for over 50 years. You can continue to rely on Advances in Immunology to provide you with critical reviews that examine subjects of vital importance to the field through summary and evaluation of current knowledge and research. The articles stress fundamental concepts, but also evaluate the experimental approaches.
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