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CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses.

ABSTRACT: Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor (PTL) are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to women who underwent PTL displayed a similar mRNA profile to that of those from term neonates. The direct contact between preterm or term neonatal CD71+ erythroid cells and maternal mononuclear immune cells, but not soluble products from these cells, induced the release of proinflammatory cytokines and a reduction in the release of TGF-?. Moreover, PTL-derived neonatal CD71+ erythroid cells (1) modestly altered CD8+ T cell activation; (2) inhibited conventional CD4+ and CD8+ T-cell expansion; (3) suppressed the expansion of CD8+ regulatory T cells; (4) regulated cytokine responses mounted by myeloid cells in the presence of a microbial product; and (5) indirectly modulated T-cell cytokine responses. In conclusion, neonatal CD71+ erythroid cells regulate neonatal T-cell and myeloid responses and their direct contact with maternal mononuclear cells induces a proinflammatory response. These findings provide insight into the biology of neonatal CD71+ erythroid cells during the physiologic and pathologic processes of labor.

SUBMITTER: Miller D

PROVIDER: S-EPMC5987205 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses.

Miller Derek D Romero Roberto R Unkel Ronald R Xu Yi Y Vadillo-Ortega Felipe F Hassan Sonia S SS Gomez-Lopez Nardhy N

Journal of leukocyte biology 20180201 4

Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor (PTL) are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to wo ...[more]

PMID: 29389020

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Project description:ObjectiveIntraamniotic inflammation/infection is the only mechanism of disease with persuasive evidence of causality for spontaneous preterm labor/delivery. Previous studies about the behavior of cytokines in preterm labor have been largely based on the analysis of the behavior of each protein independently. Emerging evidence indicates that the study of biologic networks can provide insight into the pathobiology of disease and improve biomarker discovery. The goal of this study was to characterize the inflammatory-related protein network in the amniotic fluid of patients with preterm labor.Study designA retrospective cohort study was conducted that included women with singleton pregnancies who had spontaneous preterm labor and intact membranes (n = 135). These patients were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and amniotic fluid concentration of interleukin (IL)-6 into the following groups: (1) those without intraamniotic inflammation (n = 85), (2) those with microbial-associated intraamniotic inflammation (n = 15), and (3) those with intraamniotic inflammation without detectable bacteria (n = 35). Amniotic fluid concentrations of 33 inflammatory-related proteins were determined with the use of a multiplex bead array assay.ResultsPatients with preterm labor and intact membranes who had microbial-associated intraamniotic inflammation had a higher amniotic fluid inflammatory-related protein concentration correlation than those without intraamniotic inflammation (113 perturbed correlations). IL-1β, IL-6, macrophage inflammatory protein (MIP)-1α, and IL-1α were the most connected nodes (highest degree) in this differential correlation network (degrees of 20, 16, 12, and 12, respectively). Patients with sterile intraamniotic inflammation had correlation patterns of inflammatory-related proteins, both increased and decreased, when compared to those without intraamniotic inflammation (50 perturbed correlations). IL-1α, MIP-1α, and IL-1β were the most connected nodes in this differential correlation network (degrees of 12, 10, and 7, respectively). There were more coordinated inflammatory-related protein concentrations in the amniotic fluid of women with microbial-associated intraamniotic inflammation than in those with sterile intraamniotic inflammation (60 perturbed correlations), with IL-4 and IL-33 having the largest number of perturbed correlations (degrees of 15 and 13, respectively).ConclusionsWe report for the first time an analysis of the inflammatory-related protein network in spontaneous preterm labor. Patients with preterm labor and microbial-associated intraamniotic inflammation had more coordinated amniotic fluid inflammatory-related proteins than either those with sterile intraamniotic inflammation or those without intraamniotic inflammation. The correlations were also stronger in patients with sterile intraamniotic inflammation than in those without intraamniotic inflammation. The findings herein could be of value in the development of biomarkers of preterm labor.

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CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses.

Publications

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses.

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