IL17 mediates chorioamnionitis induced lung damage

PROJECT SUMMARY Chorioamnionitis (chorio) is the most common cause of preterm birth. Chorio increases the risk for fetal and neonatal mortality and bronchopulmonary dysplasia (BPD). There are no effective therapies for preventing preterm birth, chorio, or BPD. I have previously shown that preterm birth due to chorio is propagated by IL-1

receptor-associated kinase 1 (IRAK1). Preliminary data from my human and mouse transcriptome & cytokine analysis demonstrate increased Th17 activation, and poor lung and cardiac function in mice exposed to chorio. The central hypothesis is that chorio induces specific alterations of the fetal immune system via

stimulation of the IRAK1 pathway, resulting in lung parenchymal and vascular injury. We will test the hypotheses with the following Specific Aims: Specific Aim 1: To test the hypothesis that human infants exposed to chorio have increased Th17 cell activation and subsequent pro-inflammatory cytokine generation leading to long-term adverse lung

function & pulmonary hypertension. I will conduct a prospective cohort study on 152 preterm infants (