(459) IL-11 is regulated by TGFβ in fetal membrane explants and localizes to amniotic macrophages

Thursday, February 9, 2023

4:00 PM – 5:30 PM

Objective: We have previously demonstrated that the placenta, consisting of chorionic villi and fetal membranes, is an immunoactive tissue abundant in cytokine and chemokine production. Additionally, human fetal membranes have been shown to have distinct immunologic secretory activity, with abundant secretion of the proinflammatory cytokine IL-11. The source of these cytokines and chemokines is unclear: the fetal membrane consists of cells of trophoblast etiology (chorion), epithelial cells (amnion) and an amnion mesenchymal layer with CD14+ macrophages. In this study, we investigated the tissue localization and regulation of IL-11.

Study Design: Fetal membranes were collected at cesarean section in the absence of labor or infection. Intact fetal membranes or separated amnion and chorion were used to generate conditioned media as previously described. Explants were infected with mCherry labeled L. monocytogenes or CFSE labeled S. agalactiae. Explants were collected and imaged using immunohistochemistry and confocal microscopy. Conditioned media was collected and cytokine response was measured by ELISA and Luminex profiling.

Results:

IL-11 is secreted by fetal membranes and is present in conditioned media for both amnion and chorion explants. IL-11 is secreted in higher amounts per tissue weight in the amnion. IL-11 was found to co-localize with CD14+ cells in the mesenchymal cell layer of the amnion. In response to TGFβ the amnion increases IL-11 secretion, but this was not seen with chorion explants. Accordingly, TGFβ increased IL-11 transcripts. Interestingly, TGFβ is predominantly secreted by chorion explants suggesting paracrine regulation.

Conclusion:

IL-11 secretion is uniquely regulated by TGFβ in the amnion layer of the fetal membrane and produced at high amounts in comparison to matched chorionic villi. IL-11 is secreted by the resident macrophages of the amnion in response to TGFβ and may be an important target for innate immune defense of the fetal membrane to bacterial pathogens.

Primary & Presenting Author(s)

Eva Fandozzi, BA (she/her/hers)
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States

Coauthor(s)

Caroline Smith, BA (she/her/hers)
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States
Christina J. Megli, MD, PhD
Research Assistant Professor
Magee- Womens Hospital UPMC
Pittsburgh, Pennsylvania, United States