IRF5 Signaling in Phagocytes Is Detrimental to Neonatal Hypoxic Ischemic Encephalopathy.
IRF5 Signaling in Phagocytes Is Detrimental to Neonatal Hypoxic Ischemic Encephalopathy.
复制标题
吞噬细胞中的IRF5信号传导对新生儿缺氧缺血性脑病有害。
DOI：
10.1007/s12975-020-00832-x
复制
发表时间：
2021-08
影响因子：
6.9
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Al Mamun A;Yu H;Sharmeen R;McCullough LD;Liu F
新生儿缺氧缺血性脑病（HIE）的免疫反应加剧脑损伤。包括小胶质细胞在内的吞噬细胞在免疫应答中起着核心作用，但如何调节吞噬细胞的激活仍然是一个谜。之前我们已经报道过，干扰素调节因子5 （IRF5）信号传导与成年小鼠中风后的促炎性小胶质细胞表型密切相关。本研究探讨了IRF5在hie后炎症中的调节作用。将雄性IRF5条件敲除（CKO）和出生后第10天（P10）幼崽采用Rice-Vannucci模型（RVM）诱导HIE。结果包括形态学和神经行为改变在HIE后第7天进行评估。通过流式细胞术（FC）、RT-PCR和多重细胞因子检测评估小胶质细胞/巨噬细胞表型和炎症反应。lentii -IRF5病毒用于小胶质细胞-神经元共培养，以评估缺氧（OGD）缺血性神经元中小胶质细胞IRF5上调的影响。与IRF5fl/fl对照幼崽相比，缺失吞噬性IRF5导致IRF5表达显著降低，对HIE的促炎反应减弱，抗炎反应增强，预后改善。体外慢病毒转染实验显示，IRF5在小胶质细胞中的过表达可放大促炎信号，加剧ogd诱导的神经元凋亡和神经突断裂。IRF5信号介导小胶质细胞促炎激活，也影响抗炎反应。吞噬性IRF5信号在HIE中是有害的，是缺血性炎症后的潜在治疗靶点。
Immune responses to neonatal hypoxic ischemic encephalopathy (HIE) exacerbate brain injury. Phagocytes, including microglia, play a central role in the immune response, but how the activation of phagocytes is regulated remains elusive. Previously we have reported that interferon regulatory factor 5 (IRF5) signaling is closely correlated with a pro-inflammatory microglial phenotype in adult mice after stroke. The present study investigated IRF5’s regulatory role in post-HIE inflammation. Male IRF5 conditional knockout (CKO) and IRF5fl/fl postnatal day 10 (P10) pups were subjected to the Rice-Vannucci Model (RVM) to induce HIE. Outcomes including morphological and neurobehavioral changes were evaluated at day 7 after HIE. Microglia/macrophage phenotypes and inflammatory responses were evaluated by flow cytometry (FC), RT-PCR and multiplex cytokine assays. Lenti-IRF5 virus was administered in microglia-neuron co-cultures to evaluate the effects of microglial IRF5 upregulation in ischemic neurons exposed to oxygen glucose deprivation (OGD). Deletion of phagocytic IRF5 resulted in significantly decreased IRF5 expression, attenuated pro-inflammatory and enhanced anti-inflammatory responses to HIE, and improved outcomes compared to IRF5fl/fl control pups. In vitro lentivirus transfection experiments revealed that overexpression of IRF5 in microglia amplified pro-inflammatory signals and exacerbated OGD-induced neuronal apoptosis and neurite fragmentation. IRF5 signaling mediates microglial pro-inflammatory activation and also affects anti-inflammatory responses. Phagocytic IRF5 signaling is detrimental in HIE and is a potential therapeutic target for post-ischemic inflammation.
登录
查看更多内容
干扰素调节因子 4/5 信号传导对小鼠缺血性中风后小胶质细胞活化的影响。
DOI：
10.1111/ejn.13778
发表时间：
2018-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Al Mamun A;Chauhan A;Yu H;Xu Y;Sharmeen R;Liu F
通讯作者：
Liu F
影响因子：
7.1
作者：
Holtman IR;Raj DD;Miller JA;Schaafsma W;Yin Z;Brouwer N;Wes PD;Möller T;Orre M;Kamphuis W;Hol EM;Boddeke EW;Eggen BJ
通讯作者：
Eggen BJ
影响因子：
24
作者：
Courties, Gabriel;Heidt, Timo;Sebas, Matthew;Iwamoto, Yoshiko;Jeon, Derrick;Truelove, Jessica;Tricot, Benoit;Wojtkiewicz, Greg;Dutta, Partha;Sager, Hendrik B.;Borodovsky, Anna;Novobrantseva, Tatiana;Klebanov, Boris;Fitzgerald, Kevin;Anderson, Daniel G.;Libby, Peter;Swirski, Filip K.;Weissleder, Ralph;Nahrendorf, Matthias
通讯作者：
Nahrendorf, Matthias
影响因子：
15.1
作者：
Burke, Nikita N.;Kerr, Daniel M.;Roche, Michelle
通讯作者：
Roche, Michelle
影响因子：
16.2
作者：
HSIAO, KK;BORCHELT, DR;CARLSON, G
通讯作者：
CARLSON, G