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Transitory accumulation of myeloid-derived suppressor cells in neonates is critical for maintenance of homeostasis

ABSTRACT: Myeloid-derived suppressor cells (MDSC) are potent negative regulators of immune responses at many pathological conditions. It is widely accepted that these cells are not present under steady state condition. Here, we report that MDSC with highly potent ability to suppress T cells accumulate during first two weeks of life in mice. MDSC suppressive activity in neonates was triggered by lactoferrin, a component of milk, and mediated by nitric oxide and up-regulation of PGE2 regulated by S100A9/A8 proteins. Newborn MDSC had transcriptome similar to that of tumor MDSC. However, they had strong up-regulation of antimicrobial gene network. This was associated with enhanced antimicrobial activity of these cells. MDSC played a critical role in control of experimental necrotizing enterocolitis in newborn mice. In humans, MDSC in cord blood of low-weight preterm infants prone to the development of NEC had significantly lower suppressive activity than the cells from cord blood of infants with normal weight. Thus, transitory presence of MDSC after birth is critical for the maintenance of immune homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE97993 | GEO | 2018/01/03

SECONDARY ACCESSION(S): PRJNA383586

REPOSITORIES: GEO

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Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu. Umbilical cord blood was drawn into Tempus Blood RNA tubes (Applied Biosystems) from children born between January and May 2010 at the maternity unit of Jorvi hospital (Espoo, Finland; n=48), maternity units of Tartu and PM-CM-5lva (Estonia; n=25), or two maternity departments in Petrozavodsk (capital of the Republic of Karelia, Russian Federation; n=40) according to the manufacturerM-BM-4s protocol and then stored in M-bM-^HM-^R70 M-BM-0C until analyzed. All newborn infants were full-term (>36 gestational weeks) and born vaginally. 113 cord blood RNA samples were analyzed with Affymetrix U219 gene array. Gender, pregnancy week, month of birth and HLA risk class were included as confounding factors in the analysis model.

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Transitory accumulation of myeloid-derived suppressor cells in neonates is critical for maintenance of homeostasis

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