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Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity

Abstract

There are no studies so far linking molecular regulation of lymphangiogenesis and induction of adaptive immunity. Here, we show that blockade of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling significantly suppresses corneal antigen-presenting (dendritic) cell trafficking to draining lymph nodes, induction of delayed-type hypersensitivity and rejection of corneal transplants. Regulating the function of VEGFR-3 may therefore be a mechanism for modulating adaptive immunity in the periphery.

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Figure 1: VEGFR-3 expression in corneal inflammation and mediation of corneal dendritic cell migration in culture.
Figure 2: VEGFR-3 mediates corneal dendritic cell migration to lymph nodes and induction of immunity to corneal transplant.

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Acknowledgements

We thank D. Pottle and R. Huang for technical assistance with the confocal microscopy and flow cytometry studies, D. Jackson for the antibody to LYVE-1 and R.L. Gendron for the corneal stromal fibroblasts (MK/T-1). This work is supported by National Institutes of Health/National Eye Institute Grants (M.R.D. and J.W.S.), a research grant from the Massachusetts Lions Eye Research Fund and a Special Scholar Award from Research to Prevent Blindness (M.R.D.). L.C. is supported by National Institutes of Health/Ruth L. Kirschstein National Research Service Award. C.C. is supported by Deutsche Forschungsgemeinschaft.

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Correspondence to M Reza Dana.

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Chen, L., Hamrah, P., Cursiefen, C. et al. Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat Med 10, 813–815 (2004). https://doi.org/10.1038/nm1078

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