Unraveling T-cell and endothelial cell interactions through computational analyses
Date
2023
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Publisher
University of Delaware
Abstract
A continuous challenge in drug delivery is to achieve tissue and organ-specific targeting, in particular to places like the lymph node and brain, where many difficult-to-treat diseases reside. This challenge is due to organ-specific endothelial barriers that possess unique cell membrane proteins and serve as restrictive barriers to molecules, particles, and cells moving from the systemic circulation into the tissue parenchyma. However, immune cells navigate these barriers regularly, particularly when patrolling lymph nodes and responding to brain cancer. As such, we sought to uncover unique interactions between local endothelial cells and immune counterparts to enable an analysis pipeline of tissue-specific receptor binding pairs that may ultimately advance the development of therapeutics finely tuned for precise tissue-specific targeting. This pipeline has generated preliminary data that uncovers distinct cell-cell interactions between local endothelium and T-lymphocytes across two key endothelial barriers i.e., lymph node and the blood-brain barrier, from publicly available single-cell RNA sequencing datasets through computational analyses. The differential expression analysis of HEV vs brain endothelial cells and naïve vs activated T lymphocytes led to the identification of various cell-type specific markers. The co-expression analysis revealed expression patterns of cell surface markers and identification of modules of co-expressing genes. The cell-cell communication analysis helped in identifying binding partners of markers expressed on HEV with that of naïve T lymphocytes and markers expressed on brain endothelial cells with that of activated T lymphocytes. This approach offers the opportunity to shed light on the signaling mechanisms involved in these interactions.
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Keywords
Drug delivery, Lymph node, Tissue parenchyma, Endothelial cells, Brain cancer