Regulatory T cell and endothelial cell crosstalk

Wenji Piao^{1

2}, Zachariah L Lee¹, Gregory Zapas¹, Long Wu^{1

2}, Christopher M Jewell^{3

4

5}, Reza Abdi⁶, Jonathan S Bromberg^{7

8

9}

Affiliations

¹ Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
² Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA.
³ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
⁵ Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, USA.
⁶ Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. jbromberg@som.umaryland.edu.
⁸ Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA. jbromberg@som.umaryland.edu.
⁹ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA. jbromberg@som.umaryland.edu.

PMID: 40169744
DOI: 10.1038/s41577-025-01149-2

Review

Regulatory T cell and endothelial cell crosstalk

Wenji Piao et al. Nat Rev Immunol. 2025 Aug.

. 2025 Aug;25(8):588-607.

doi: 10.1038/s41577-025-01149-2. Epub 2025 Apr 1.

Authors

Wenji Piao^{1

2}, Zachariah L Lee¹, Gregory Zapas¹, Long Wu^{1

2}, Christopher M Jewell^{3

4

5}, Reza Abdi⁶, Jonathan S Bromberg^{7

8

9}

Affiliations

¹ Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
² Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA.
³ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
⁵ Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, USA.
⁶ Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. jbromberg@som.umaryland.edu.
⁸ Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA. jbromberg@som.umaryland.edu.
⁹ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA. jbromberg@som.umaryland.edu.

PMID: 40169744
DOI: 10.1038/s41577-025-01149-2

Abstract

Regulatory T (T_reg) cells have a central role in the maintenance of immune surveillance and tolerance. They can migrate from lymphoid organs to blood and then into tissues and egress from tissues into draining lymph nodes. Specialized endothelial cells of blood and lymphatic vessels are the key gatekeepers for these processes. T_reg cells that transmigrate across single-cell layers of endothelial cells engage in bidirectional crosstalk with these cells and regulate vascular permeability by promoting structural modifications of blood and lymphatic endothelial cells. In turn, blood and lymphatic endothelial cells can modulate T_reg cell recirculation and residency. Here, we discuss recent insights into the cellular and molecular mechanisms of the crosstalk between T_reg cells and endothelial cells and explore potential therapeutic strategies to target these interactions in autoimmunity, transplantation and cancer.

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Conflict of interest statement

Competing interests: C.M.J. is an employee of the VA Maryland Health Care System. The views reported in this article do not reflect the views of the Department of Veterans Affairs or the United States Government. C.M.J. has an equity position with Barinthus Biotherapeutics and Cartesian Therapeutics. The other authors declare no competing interests.

References

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Regulatory T cell and endothelial cell crosstalk

Affiliations

Regulatory T cell and endothelial cell crosstalk

Authors

Affiliations

Abstract

Conflict of interest statement

References

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