Neuropilin-1^(high) monocytes protect against neonatal inflammation  

作　　者：Xiaoqing Zheng Wen Lei Yongmei Zhang Han Jin Cha Han Fan Wu Chonghong Jia Ruihong Zeng Zhanghua Chen Yuxia Zhang Haitao Wang Qiang Liu Zhi Yao Ying Yu Jie Zhou 

机构地区：[1]Tianjin Institute of Immunology,Key Laboratory of Immune Microenvironment and Disease(Ministry of Education),The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics,International Joint Laboratory of Ocular Diseases(Ministry of Education),State Key Laboratory of Experimental Hematology,Department of Immunology,Tianjin Medical University,Tianjin,300070,China [2]Institute of Pediatric Health and Disease,Guangdong Provincial Key Laboratory of Major Obstetric Diseases,Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou,510150,China [3]Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province,Department of Immunology,Hebei Medical University,Shijiazhuang,050017,China [4]Pediatric Immunity and Healthcare Biomedical Co.,Ltd,Guangzhou,510320,China [5]Department of Neurology,Institute of Neuroimmunology,Tianjin Medical University General Hospital,Tianjin,300052,China [6]Department of Gynecology and Obstetrics,Tianjin Medical University General Hospital,Tianjin,300052,China [7]Department of Neonatology,Guangzhou Key Laboratory of Neonatal Intestinal Diseases,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou,510150,China [8]Department of Gastroenterology,Guangzhou Institute of Pediatrics,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou,510623,China [9]Department of oncology,The Second Hospital of Tianjin Medical University,Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases,Tianjin,300211,China [10]Department of Pharmacology,Tianjin Key Laboratory of Inflammatory Biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin,300070,China

出　　处：《Cellular & Molecular Immunology》2024年第6期575-588,共14页中国免疫学杂志（英文版）

基　　金：National Natural Science Foundation of China(No.81925018 and 82130049 to J.Zhou;No.82001660 to X.Zheng);China Postdoctoral Science Foundation(No.2021M692406 to X.Zheng).

摘　　要：Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis(NEC)due to their immature immune system.The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates,yet the underlying mechanisms of which remain poorly understood.In this study,we identified a subset of neonatal monocytes characterized by high levels of neuropilin-1(Nrp1),termed Nrp1^(high) monocytes.Compared with their Nrp1low counterparts,Nrp1^(high) monocytes displayed potent immunosuppressive activity.Nrp1 deficiency in myeloid cells aggravated the severity of NEC,whereas adoptive transfer of Nrp1^(high) monocytes led to remission of NEC.Mechanistic studies showed that Nrp1,by binding to its ligand Sema4a,induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4.KLF4 transactivated Nos2 and enhanced the production of nitric oxide(NO),a key mediator of immunosuppression in monocytes.These findings reveal an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for treating inflammatory disorders in neonates.

关 键 词：Infant immunity INFLAMMATION MONOCYTES NEUROPILIN-1 

分 类 号：R722.1[医药卫生—儿科]