期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 19, 期 9, 页码 2446-2456出版社
WILEY
DOI: 10.1111/ajt.15331
关键词
basic (laboratory) research; science; chemokines; chemokine receptors; corneal transplantation; ophthalmology; cytokines; cytokine receptors; dendritic cell; immunosuppression; immune modulation; translational research; science; vascular biology
资金
- Deutsche Forschungsgemeinschaft [FOR2240/BO 4489/1-1 (AS, FB) & Cu 47/4-2 (CC)] Funding Source: Medline
- Center for Molecular Medicine Cologne, University of Cologne Funding Source: Medline
- German Cancer Aid (Deutsche Krebshilfe) (RR) Funding Source: Medline
The microenvironment plays an important role in several immunological processes. Vascular endothelial growth factor-A (VEGF-A) not only regulates angiogenesis, but is known as a modulator of the immune microenvironment. Modulating the site of transplantation might be beneficial for subsequent transplant survival. In this study, we therefore analyzed the effect that a local blockade of VEGF-A in the inflamed cornea as the graft receiving tissue has on the immune system. We used the murine model of suture-induced neovascularization and subsequent high-risk corneal transplantation, which is an optimal model for local drug application. Mice were treated with VEGFR1/R2 trap prior to transplantation. We analyzed corneal gene expression, as well as protein levels in the cornea and serum on the day of transplantation, 2 and 8 weeks later. Local VEGF depletion prior to transplantation increases the expression of pro-inflammatory as well as immune regulatory cytokines only in the corneal microenvironment, but not in the serum. Furthermore, local VEGFR1/R2 trap treatment significantly inhibits the infiltration of CD11c+ dendritic cells into the cornea. Subsequent increased corneal transplantation success was accompanied by a local upregulation of Foxp3 gene expression. This study demonstrates that locally restricted VEGF depletion increases transplantation success by modulating the receiving corneal microenvironment and inducing tolerogenic mechanisms.
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