Mechanisms regulating transitory suppressive activity of neutrophils in newborns: PMNs-MDSCs in newborns

Author:

Perego Michela1,Fu Shuyu1,Cao Yingjiao23,Kossenkov Andrew1,Yao Meng2,Bonner Erin1,Alicea-Torres Kevin14,Liu Wangkai5,Jiang Zhilong6,Chen Zhihong6,Fuchs Serge Y7,Zhou Jie2,Gabrilovich Dmitry I8

Affiliation:

1. The Wistar Institute , Philadelphia, Pennsylvania, USA

2. Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Sciences, Tianjin Medical University , Tianjin, China

3. Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China

4. Biology Department, University of Puerto Rico-Humacao , Humacao, Puerto Rico, USA

5. Department of Pediatrics, First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China

6. Department of Respiratory and Critical Care Medicine, Zhongshan Hospital; Shanghai Institute of Respiratory Disease, Fudan University , Shanghai, China

7. Department of Biomedical Sciences, School of Veterinary Medicine University of Pennsylvania , Philadelphia, Pennsylvania, USA

8. AstraZeneca , Gaithersburg, Maryland, USA

Abstract

Abstract Transitory appearance of immune suppressive polymorphonuclear neutrophils (PMNs) defined as myeloid-derived suppressor cells (PMNs-MDSCs) in newborns is important for their protection from inflammation associated with newly established gut microbiota. Here, we report that inhibition of the type I IFN (IFN1) pathway played a major role in regulation of PMNs-MDSCs-suppressive activity during first weeks of life. Expression of the IFN1 receptor IFNAR1 was markedly lower in PMNs-MDSCs. However, in newborn mice, down-regulation of IFNAR1 was not sufficient to render PMNs immune suppressive. That also required the presence of a positive signal from lactoferrin via its receptor low-density lipoprotein receptor-related protein 2. The latter effect was mediated via NF-κB activation, which was tempered by IFN1 in a manner that involved suppressor of cytokine signaling 3. Thus, we discovered a mechanism of tight regulation of immune suppressive PMNs-MDSCs in newborns, which may be used in the development of therapies of neonatal pathologies.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Immunology,Immunology and Allergy

Reference49 articles.

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3. Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses;Rieber;Clinical and Experimental Immunology,2013

4. Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period;Schwarz;Clinical and Experimental Immunology,2018

5. Murine myeloid-derived suppressor cells are a source of elevated levels of interleukin-27 in early life and compromise control of bacterial infection;Parson;Immunol Cell Biol,2019

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. PMN-MDSC in newborns: Regulation of the regulators;Journal of Leukocyte Biology;2022-08-10

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