PI3K信号过度活化引发免疫病理机制研究进展  

Advances on immune pathology mechanism of overactivation of PI3K signal pathway

作　　者：王燕[1,2] 周远涛[2] 张玉 贺晓丽[2] 陶律延 李莉 WANG Yan;ZHOU Yuantao;ZHANG Yu;HE Xiaoli;TAO Lyuyan;LI Li(Children's Hospital Affiliated to Kunming Medical University,Kunming 650228,China;Kunming Children's Hospital,Institution of Pediatrics Research,Yunnan Key Laboratory of Children's Major Disease Research,Kunming 650228,China)

机构地区：[1]昆明医科大学附属儿童医院,昆明650228 [2]昆明市儿童医院,云南省儿科研究所,云南省儿童重大疾病研究重点实验室,昆明650228

出　　处：《中国免疫学杂志》2024年第7期1536-1541,1547,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金(81960294,81560262);云南省基础研究面上项目(202101AT070231);云南省中青年学术和技术带头人后备人才项目(202105AC160012);云南省高层次卫生技术人才(医学学科带头人)培养计划(D-2019-017);云南省科技厅基础研究重点项目(202401AS070008);昆明市卫生科技人才培养项目暨“十百千”工程培养计划[2020-SW(国)-11]。

摘　　要：目前少数研究发现磷脂酰肌醇3-激酶(PI3K)基因PIK3CD(编码p110δ)发生功能获得性(GOF)变异后,可导致活化的PI3Kδ综合征(APDS)。该突变可通过诱导T细胞减少/衰老/耗竭、B细胞发育受阻、NK细胞毒性降低等多种免疫系统内部缺陷机制导致机体内免疫缺陷、免疫失调甚至肿瘤发生。本文主要对PI3Kδ GOF诱导APDS发生的相关临床疾病特点及免疫缺陷分子机制展开综述,重点阐述该突变导致淋巴细胞发育、分化及功能缺陷的分子机制。At present,some studies have identified gain-of-function(GOF)mutations in phosphoinositide 3-kinase(PI3K)genes PIK3CD(which encodes p110δ)lead to activated PI3Kδsyndrome(APDS),which can cause immune deficiency,immune disorder and even tumor by multiple mechanisms of internal immune system defects,such as reduction/senescence/depletion of T cells,impaired development of B cells,and reduced toxicity of NK cells.Here,we review clinical characteristics of APDS induced by PI3KδGOF and molecular mechanism of immune deficiency,focusing on molecular mechanism of lymphocyte development,differentiation and functional defects caused by GOF mutation.

关 键 词：磷脂酰肌醇3-激酶(PI3K) PI3Kδ功能获得性变异 活化的PI3Kδ综合征(APDS) 淋巴细胞缺陷 免疫病理 

分 类 号：R392.3[医药卫生—免疫学]