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Review
. 2025 Feb 4:4:1518772.
doi: 10.3389/frtra.2025.1518772. eCollection 2025.

Immunomodulation by allograft endothelial cells

Sayantan Bose  1   2   3   4 , Vicki Do  1   2 , Chiara Testini  1   2   3   4 , Suchita S Jadhav  1   2   3   4 , Nicolas Sailliet  1   2   3   4 , Alvin T Kho  1   3   4   5 , Masaki Komatsu  1   2   3   4 , Leo Boneschansker  1   2   3   4 , Sek Won Kong  1   3   4   5 , Johannes Wedel  1   2   3   4   5 , David M Briscoe  1   2   3   4
Affiliations
Review

Immunomodulation by allograft endothelial cells

Sayantan Bose et al. Front Transplant. .

Abstract

It is increasingly appreciated that the expression of immunoregulatory molecules within tumors have potential to shape a microenvironment that promotes local immunoevasion and immunoregulation. However, little is known about tissue-intrinsic immunomodulatory mechanisms following transplantation. We propose that differences in the phenotype of microvascular endothelial cells impact the alloantigenicity of the graft and its potential to promote immunoregulation following transplantation. We focus this review on the concept that graft-dependent immunoregulation may evolve post-transplantation, and that it is dependent on the phenotype of select subsets of intragraft endothelial cells. We also discuss evidence that long-term graft survival is critically dependent on adaptive interactions among immune cells and endothelial cells within the transplanted tissue microenvironment.

Keywords: allograft (ALLO); endothelial cell; graft survival; immunoregulation; transplantation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Cartoon illustration of how the phenotype of intragraft endothelial cell subsets regulate local alloimmunity to promote graft-dependent immunoregulation.
Figure 2
Figure 2
Intragraft microvascular endothelial cell heterogeneity from murine cardiac allo- and iso grafts. Single cell RNA-sequencing data from post-transplant day 5 murine cardiac isografts (Balb/c → Balb/c, n = 2) and allografts (Balb/c → C57BL6, n = 2) were downloaded from the NCBI GEO (accession number: GSE151048) (79). Seurat objects were generated from each sample, integrated using Harmony, and cluster resolution determined using the Clustree method (–83). EC were identified using Pecam1 and Cdh5 expression and were clustered to identify subsets using selected EC annotation transcripts (57, 62, 80, 81). (A) UMAP scatter plot, color-coded for EC subclusters. EC were clustered based on established arterial, venous and capillary gene expression; a total of 12 capillary subsets are color coded. (B) Dot plot illustrating the transcripts used for EC subset annotation. The percent and level of expression of each transcript is illustrated by the size and color (blue) of each dot. (C) Feature and Violin plots of intragraft EC subsets isolated from isografts (left panels) or allografts (right panels) depicting select transcript expression of pro-inflammatory (VCAM-1), immunoregulatory (PD-L1) and immunoevasive (Sema3F) molecules. The color (blue dot) illustrates the level of expression of each gene in each Feature plot. Violin plots illustrate the relative level of expression of each gene in each EC subset.
Figure 3
Figure 3
Pseudospatial expression of proinflammatory, immunoregulatory and immunoevasive transcripts in intragraft endothelial cells. A pseudotime estimation method was used to generate a pseudospatial resolution of single cell RNA-sequencing data from Figure 2 within the microvascular bed (84). The spatial trajectory starts in arterial microvasculature (as shown in Figure 2A), passes through capillaries and ends in venous EC subsets. (A) UMAP scatter plot color coded for the pseudospace. The trajectory is highlighted. (B) Schematic representation of the pseudospace within the microvasculature. (C) Scatter plots of isografts (left; green) and allografts (right; orange) depicting patterns of select proinflammatory (CXCL9, CXCL-10 and VCAM-1) or immunoregulatory/immunoevasive (PD-L1, Semaphorin3F) transcript expression over the pseudospace within each EC subset. Each line (green, isograft vs. orange, allograft) represents the average transcript expression within EC subsets along the pseudospace.
Figure 4
Figure 4
Cartoon illustration of the four patterns of leukocyte migration (96).
See this image and copyright information in PMC

References

    1. Nankivell BJ, Alexander SI. Rejection of the kidney allograft. N Engl J Med. (2010) 363(15):1451–62. 10.1056/NEJMra0902927 - DOI - PubMed
    1. Ingulli E, Alexander SI, Briscoe DM. Immunology of pediatric renal transplantation. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein SL, editors. Pediatric Nephrology. New York, NY: Springer; (2016). p. 2457–500.
    1. Zhang X, Reed EF. Effect of antibodies on endothelium. Am J Transplant. (2009) 9(11):2459–65. 10.1111/j.1600-6143.2009.02819.x - DOI - PMC - PubMed
    1. Rothstein DM, Sayegh MH. T-cell costimulatory pathways in allograft rejection and tolerance. Immunol Rev. (2003) 196:85–108. 10.1046/j.1600-065X.2003.00088.x - DOI - PubMed
    1. Li XC, Turka LA. An update on regulatory T cells in transplant tolerance and rejection. Nat Rev Nephrol. (2010) 6(10):577–83. 10.1038/nrneph.2010.101 - DOI - PubMed

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