Trophoblasts of the human placenta directly communicate with tissue-resident T cells to shape their response to inflammation 4150
Year: 2025
Type: article
Study design: Observational Study
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)
Source: The Journal of Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416451500
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