Mechanisms regulating transitory suppressive activity of neutrophils in newborns: PMNs-MDSCs in newborns. Issue 5 (21st June 2022)

• Record Type: Journal Article
• Authors: Perego, Michela; Fu, Shuyu; Cao, Yingjiao; Kossenkov, Andrew; Yao, Meng; Bonner, Erin; Alicea-Torres, Kevin; Liu, Wangkai; Jiang, Zhilong; Chen, Zhihong; Fuchs, Serge Y; Zhou, Jie; Gabrilovich, Dmitry I
• Is Part Of: Journal of leukocyte biology. Volume 112:Issue 5(2022)
• Page Start: 955
• Page End: 968
• Publication Date: 2022-06-21
• Subjects: lactoferrin -- NF-κB -- SOCS3 -- type I IFN; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.4HI0921-514RR
• Languages: English
• ISSNs: 0741-5400

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. Graphical Abstract: A mechanism of temporal control of PMN-MDSC in newborns identified that involves lactoferrin mediated positive and type I interferon mediated negative regulation.