Endothelial Cell Modulation of T Cell Immunity

Endothelial cells form the innermost lining of blood vessels and serve as active regulators of immune function by orchestrating T cell recruitment, activation and differentiation. Far from being a passive barrier, the endothelium expresses adhesion molecules, chemokines and antigen‐presentation machinery that guide T cells across the vascular wall into inflamed or tumour‐bearing tissues. In addition, endothelial cells display co‐stimulatory and co‐inhibitory ligands, including immune checkpoints such as PD‐L1, which fine‐tune T cell receptor signalling and effector responses. Mechanical forces, metabolic shifts and the local cytokine milieu further shape endothelial immunoregulatory programmes, enabling context‐dependent promotion of tolerance or immunity. This interplay has profound implications for host defence, chronic inflammation, cancer immunosurveillance and transplant rejection. By modulating glycolytic pathways, antigen‐processing complexes and checkpoint ligand expression, endothelial cells can suppress cytotoxic CD8+ T cells or enhance regulatory T cell function, thereby influencing the outcome of anti‐tumour therapies, vascular inflammation and autoimmunity. Understanding the molecular circuits that govern endothelial–T cell crosstalk offers new avenues for therapeutic intervention, ranging from blockade of inhibitory receptors to metabolic reprogramming of the vascular niche.

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Endothelial Cell Modulation of T Cell Immunity publication trend

The graph below shows the total number of articles in endothelial cell modulation of t cell immunity across all publications each year (not limited to Nature Index journals).

Technical terms

Endothelial cell: A specialised cell forming the inner lining of blood vessels that regulates vascular tone, permeability and immune cell trafficking.

PD-L1: Programmed death-ligand 1, an immune checkpoint protein expressed on various cells, including endothelium, that binds PD-1 on T cells to inhibit their activity.

Integrin αVβ3: A heterodimeric adhesion receptor on endothelial cells that transduces mechanical signals and mediates interactions with the extracellular matrix.

Transmural flow: Movement of fluid across the vessel wall driven by pressure differences, influencing endothelial phenotype and gene expression.

TNF receptor 2 (TNFR2): A membrane receptor for tumour necrosis factor that modulates inflammatory signalling and metabolic pathways in endothelial cells.

Glycolysis: The metabolic pathway by which glucose is converted to pyruvate, providing energy and biosynthetic precursors, and regulating endothelial immunomodulatory capacity.

Co-stimulatory molecules: Surface ligands on antigen-presenting cells, including endothelium, that provide essential secondary signals to optimise T cell activation and differentiation.

References

1. Transmural Flow Upregulates PD‐L1 Expression in Microvascular Networks. Advanced Science (2024).
2. Exploring the crosstalk between endothelial cells, immune cells, and immune checkpoints in the tumor microenvironment: new insights and therapeutic implications. Cell Death & Disease (2023).
3. Tumor necrosis factor receptor 2 promotes endothelial cell-mediated suppression of CD8+ T cells through tuning glycolysis in chemoresistance of breast cancer. Journal of Translational Medicine (2024).
4. T Lymphocyte–Endothelial Interactions: Emerging Understanding of Trafficking and Antigen-Specific Immunity. Frontiers in Immunology (2015).
5. Antigen Presentation by Vascular Cells. Frontiers in Immunology (2017).
6. Human Endothelial Cells Modulate CD4+ T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity. Frontiers in Immunology (2018).
7. IFNγ, and to a Lesser Extent TNFα, Provokes a Sustained Endothelial Costimulatory Phenotype. Frontiers in Immunology (2021).
8. Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes. Frontiers in Immunology (2022).