Neuropilin-1high monocytes protect against neonatal inflammation

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

doi:10.1038/s41423-024-01157-7

Neuropilin-1^high monocytes protect against neonatal inflammation

Cell Mol Immunol. 2024 Apr 17. doi: 10.1038/s41423-024-01157-7. Online ahead of print.

Authors

Xiaoqing Zheng^#^{1

2

3}, Wen Lei^#⁴, Yongmei Zhang^#¹, Han Jin⁵, Cha Han⁶, Fan Wu^{2

7}, Chonghong Jia^{2

7}, Ruihong Zeng³, Zhanghua Chen⁸, Yuxia Zhang⁸, Haitao Wang⁹, Qiang Liu⁵, Zhi Yao¹, Ying Yu¹⁰, Jie Zhou¹¹

Affiliations

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.
¹¹ 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. zhoujie@tmu.edu.cn.

^# Contributed equally.

PMID: 38632385
DOI: 10.1038/s41423-024-01157-7

Abstract

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 Nrp1^low 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.

Keywords: Infant immunity; Inflammation; Monocytes; Neuropilin-1.

Abstract

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