Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates

Abstract

Regulatory T-cells (Treg) have a protective role for the control of immune activation and tissue damage. The effects of chorioamnionitis (chorio) on Treg in moderate/late preterm newborns are not known. We hypothesized that infants exposed to chorio would have decreased Treg frequency and/or function. We isolated mononuclear cells from adult peripheral blood and cord blood from term and moderate/late preterm infants who were classified for severity of chorio exposure. Mononuclear cells were analyzed by flow cytometry for Treg frequency and phenotype. Treg suppression of activation of conventional T-cells (Tcon) was also quantified. Treg frequencies were similar in all groups of neonates, but lower than that found in adults. Newborn Treg had a naïve phenotype, with decreased levels of CD45RO, HLA-DR, CD39 and TIGIT compared to adult Treg and chorio did not affect the phenotype. Treg from preterm newborns exposed to severe chorio had higher expression of Ki67 compared to the other groups. Treg from preterm newborns were less suppressive than Treg from adults or term, and the level of suppression was reduced with severe chorio. Relative to term, Treg frequency and phenotype were not affected by prematurity and chorio but their functionality was decreased. Lower Treg activity may contribute to inflammation in newborns that is often associated with chorioamnionitis.

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants

“…IL-6 is known to skew the development of T-cell precursors to the proinflammatory Th17/Th22 cells rather than the antiinflammatory T-regulatory cells (Tregs) (44,45). We found that in a subset of infants from our cohort, cord blood Tregs from preterm infants had lower suppression of allogeneic T cells than infants, and cases with severe chorioamnionitis had lower Treg suppressive effects than gestationmatched preterm infants without exposure to chorioamnionitis (46). Thus, prenatal exposure to chorioamnionitis may result in alterations of the infant immune system via IL-6-mediated inflammation and inhibition of Treg function predisposing to later respiratory disease.…”

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

“…The fetus inspires, swallows, and is bathed in amniotic fluid; therefore, the fetal lungs (68,69), gastrointestinal tract (70,71), and skin (72) are primary sites of inflammation-mediated injury. Exposure to inflammatory mediators may also occur via the placental-fetal circulation, resulting in immunomodulation within the fetal blood (73)(74)(75), lymphoid tissues (76)(77)(78), and distant organs such as the brain (79,80). The systemic response of the fetus to chorioamnionitis, termed the fetal inflammatory response syndrome (FIRS), is a severe inflammatory condition that is characterized by elevated inflammatory cytokines within fetal plasma, particularly IL-6 (81,82), and increased fetal plasma white blood cell counts (83).…”

Flow-based sorting of neonatal lymphocyte populations for transcriptomics analysis

“…Our group and others have shown that alterations in the CD4+ T cell compartment are observed in infants who are born prior to term, in the presence of inflammatory conditions, or who develop the lung disease bronchopulmonary dysplasia (Misra et al, 2015; Rueda et al, 2015). Better understanding of prematurity-related alterations in the immune system associated with disease-specific pathophysiology could lead to identification of molecular markers for diseases of preterm infants and could reveal new targets for treating inflammatory respiratory disease (Misra, 2014).…”