Trophoblasts of the human placenta directly communicate with tissue-resident T cells to shape their response to inflammation 4150

Abstract Description Tissues and immune cells are thought to communicate during health and disease. However, the nature of these signals is poorly understood. Defining tissue-T cell communication in healthy vs acutely inflamed human tissue has been particularly challenging due to the necessity for well-controlled cohorts and inflammation etiology. Using single-cell and machine learning-based analysis strategies, we examined tissue-T cell communication at the maternal-fetal interface using placentas from full-term pregnancies that are either healthy or diagnosed with intra-amniotic inflammation (IAI). We measured broad transcriptional changes in tissue cytotrophoblasts (CTBs) from the IAI cohort compared to the healthy cohort that are indicative of a response to inflammatory cytokines such as interferon. We similarly observed broad transcriptional changes in the myeloid cell compartment, indicative of inflammation-driven activation. In stark contrast, tissue resident memory T cells (Trm) did not acquire effector properties or show other signs of activation. We observed a marked change in CTB-Trm communication during IAI indicating CTBs engage several inhibitory pathways to prevent Trm activation. Taken together, our data demonstrate a disconnect in the activation status of tissue and myeloid cells, and the Trm compartment. We propose that this is due to tissue-mediated silencing of the Trm, indicating that tissue cells are capable of directing immune function in an immune-subset specific manner. Funding Sources Hartwell Foundation Postdoctoral Fellowship Topic Categories Mucosal and Regional Immunology (MUC)