Augmented Th17-Type Immune Responses in Preterm Neonates Exposed to Histologic Chorioamnionitis: Chorioamnionitis and Th17-type immunity

BACKGROUND: Histologic chorioamnionitis (HCA) is a placental inflammatory disorder that frequently precedes preterm delivery. HCA increases risk for long-standing inflammatory injury and may influence immune programming, particularly in preterm (PT) neonates. We hypothesized that HCA exposure is associated with an increased circulating frequency of pro-inflammatory, Th17-type responses. METHODS: Placental cord blood was collected from HCA-exposed or control neonates (23-41 weeks gestation). Frequencies of Th17 and T regulatory (Treg) cells and assessments of Th17-type features in CD4 and Treg cells were determined by flow cytometric analysis. RESULTS: Cord blood samples from 31 PT and 17 term neonates were analyzed by flow cytometry. A diagnosis of HCA in extremely PT (EPT, GA ≤ 30 wk) gestations was associated with the highest cord blood frequencies of progenitor (pTh17, CD4(+)CD161(+)) and mature (mTh17, CD4(+)CD161(+)CCR6(+)) Th17 cells. Preterm neonates exposed to HCA also exhibited elevated cord blood frequencies of IL-17(+) Treg cells, as well as T cells with effector memory phenotype (TEM) that co-expressed Th17-type surface antigens. CONCLUSION: Th17-type responses are amplified in preterm neonates exposed to HCA. We speculate that a Th17 bias may potentiate the inflammatory responses and related morbidity observed in preterm neonates whose immune systems have been ‘primed’ by HCA exposure.