(46) The Role of IL-9 in Preterm Birth

Background: Preterm birth is the outcome of 1 in every 10 pregnancies and is responsible for 75-80% of neonatal deaths. The multifaceted disease processes underlying preterm birth complicate its study. However, alterations in the maternal immune system are present in some subsets of preterm birth and are hypothesized to play a mechanistic role. Interleukin-9 (IL-9) is the most abundant cytokine at the maternal fetal interface and is a significant component of the immune milieu of pregnancy. Increased IL-9 signaling is reported in models of preterm birth, yet what role IL-9 signaling plays in preterm birth is not known.

Objectives: We hypothesize that increased IL-9 signaling is present and integral to the pathophysiology of immune-mediated preterm birth.

Design/Methods: We implemented a previously published murine model of immune-mediated preterm birth by Treg depletion in the 3rd week of an allogeneic pregnancy. We then used flow cytometry, ELISA, and qPCR to characterize expression of IL-9, IL-9 receptor and downstream targets in maternal and fetal tissues. Additionally, publicly available RNAseq data were analyzed for alterations in IL-9 signaling in pregnancies affected by preterm birth.

Results: Depletion of Tregs in the third week of murine pregnancy results in a decreased gestational duration. Treg-depleted pregnant dams exhibit increased expression of IL-9, IL-9r, and Arginase-1 all of which indicate increased IL-9 signaling. Furthermore, the amniotic fluid of fetuses in a Treg-depleted pregnancy contains increased levels of IL-9. RNAseq data from human pregnancies shows evidence of increased IL-9 signaling and downstream pathways indicating potential physiologic relevance of these observations.

Conclusion: Using a model of immune-mediated preterm birth, we have shown that increases in IL-9 and its downstream signaling targets are associated with decreased gestational duration. Future work will focus on elucidating the underlying mechanism to improve our understanding of immune-mediated preterm birth and identify potential targets and/or biomarkers for future studies.