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Mechanisms regulating transitory suppressive activity of neutrophils in newborns

ABSTRACT: Transitory appearance of immune suppressive polymorphonuclear neutrophils (PMN) defined as myeloid-derived suppressor cells (PMN-MDSC) in newborns is important for their protection from inflammation associated with newly established gut microbiota. Here, we report that inhibition of the type I interferon (IFN1) pathway played a major role in regulation of PMN-MDSC suppressive activity during first weeks of life. Expression of the IFN1 receptor IFNAR1 was markedly lower in PMN-MDSC. However, in newborn mice, down-regulation of IFNAR1 was not sufficient to render PMN immune suppressive. That also required the presence of a positive signal from lactoferrin via its receptor LRP2. The latter effect was mediated via NF-kB activation, which was tempered by IFN1 in a manner that involved SOCS3. Thus, we discovered a mechanism of tight regulation of immune suppressive PMN-MDSC in newborns, which may be used in the development of therapies of neonatal pathologies

ORGANISM(S): Mus musculus

PROVIDER: GSE202264 | GEO | 2022/05/31

REPOSITORIES: GEO

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