Inflammation at the maternal-fetal Interface disrupts regulatory T cell function in a mouse model of ascending chorioamnionitis 4541

Abstract Description Chorioamnionitis, defined as an infection and/or inflammation of the maternal and fetal membranes, remains a leading cause of preterm birth (PTB). This is largely due to limitations of current diagnostics, which detect inflammation only after significant maternal and fetal tissue damage occurs. This highlights the need for preventive strategies to sustain the immunosuppressive state at the maternal-fetal interface (MFI). Regulatory T cells (Tregs) are key to maintaining this immunosuppressive state. However, the precise mechanism by which inflammation at the MFI impacts Tregs remains incompletely described. To address this, we utilized a mouse model of ascending chorioamnionitis. E14.5 C57BL/6 dams were intravaginally inoculated with 100 CFU of E. coli K1 or PBS (control). Eighteen hours post inoculation, decidual tissues (MFI) were harvested and analyzed via flow cytometry to assess immune cell phenotype. We found that Tregs were depleted at the MFI following intravaginal E. coli inoculation. Interestingly, inflammation at the MFI strongly impacted Treg function, with a significant reduction in TGF-β1 and IL-10 production. This resulted in leukocyte infiltration and activation, heightened inflammation, early onset labor and ultimately PTB. Future studies will investigate how inflammation at the MFI impacts Tregs stability, including a potential shift to a pro-inflammatory “ex-Treg” phenotype. This work highlights how inflammation disrupts immune tolerance at the MFI. Funding Sources Supported by R01 AI 141673 Topic Categories Mucosal and Regional Immunology (MUC)