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Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival

PURPOSE: The lymphatic pathway mediates transplant rejection. We recently reported that lymphatic vessels develop luminal valves in the cornea during lymphangiogenesis, and these valves express integrin alpha 9 (Itga-9) and play a critical role in directing lymph flow. In this study, we used an allo...

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Autores principales: Kang, Gyeong Jin, Truong, Tan, Huang, Eric, Su, Valerie, Ge, Shaokui, Chen, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096415/
https://www.ncbi.nlm.nih.gov/pubmed/27806381
http://dx.doi.org/10.1167/iovs.16-20130
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author Kang, Gyeong Jin
Truong, Tan
Huang, Eric
Su, Valerie
Ge, Shaokui
Chen, Lu
author_facet Kang, Gyeong Jin
Truong, Tan
Huang, Eric
Su, Valerie
Ge, Shaokui
Chen, Lu
author_sort Kang, Gyeong Jin
collection PubMed
description PURPOSE: The lymphatic pathway mediates transplant rejection. We recently reported that lymphatic vessels develop luminal valves in the cornea during lymphangiogenesis, and these valves express integrin alpha 9 (Itga-9) and play a critical role in directing lymph flow. In this study, we used an allogeneic corneal transplantation model to investigate whether Itga-9 blockade could suppress valvulogenesis after transplantation, and how this effect would influence the outcomes of the transplants. METHODS: Orthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice. The recipients were randomized to receive subconjunctival injections of either Itga-9 blocking antibody or isotype control twice a week for 8 weeks. Corneal grafts were assessed in vivo by ophthalmic slit-lamp biomicroscopy and analyzed using Kaplan-Meier survival curves. Additionally, whole-mount full-thickness corneas were evaluated ex vivo by immunofluorescent microscopy on both lymphatic vessels and valves. RESULTS: Anti–Itga-9 treatment suppressed lymphatic valvulogenesis after transplantation. Our treatment did not affect lymphatic vessel formation or their nasal polarized distribution in the cornea. More importantly, Itga-9 blockade led to a significant promotion of graft survival. CONCLUSIONS: Lymphatic valvulogenesis is critically involved in transplant rejection. Itga-9 targeting may offer a new and effective strategy to interfere with the immune responses and promote graft survival.
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spelling pubmed-50964152016-11-06 Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival Kang, Gyeong Jin Truong, Tan Huang, Eric Su, Valerie Ge, Shaokui Chen, Lu Invest Ophthalmol Vis Sci Cornea PURPOSE: The lymphatic pathway mediates transplant rejection. We recently reported that lymphatic vessels develop luminal valves in the cornea during lymphangiogenesis, and these valves express integrin alpha 9 (Itga-9) and play a critical role in directing lymph flow. In this study, we used an allogeneic corneal transplantation model to investigate whether Itga-9 blockade could suppress valvulogenesis after transplantation, and how this effect would influence the outcomes of the transplants. METHODS: Orthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice. The recipients were randomized to receive subconjunctival injections of either Itga-9 blocking antibody or isotype control twice a week for 8 weeks. Corneal grafts were assessed in vivo by ophthalmic slit-lamp biomicroscopy and analyzed using Kaplan-Meier survival curves. Additionally, whole-mount full-thickness corneas were evaluated ex vivo by immunofluorescent microscopy on both lymphatic vessels and valves. RESULTS: Anti–Itga-9 treatment suppressed lymphatic valvulogenesis after transplantation. Our treatment did not affect lymphatic vessel formation or their nasal polarized distribution in the cornea. More importantly, Itga-9 blockade led to a significant promotion of graft survival. CONCLUSIONS: Lymphatic valvulogenesis is critically involved in transplant rejection. Itga-9 targeting may offer a new and effective strategy to interfere with the immune responses and promote graft survival. The Association for Research in Vision and Ophthalmology 2016-11 /pmc/articles/PMC5096415/ /pubmed/27806381 http://dx.doi.org/10.1167/iovs.16-20130 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Cornea
Kang, Gyeong Jin
Truong, Tan
Huang, Eric
Su, Valerie
Ge, Shaokui
Chen, Lu
Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival
title Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival
title_full Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival
title_fullStr Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival
title_full_unstemmed Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival
title_short Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival
title_sort integrin alpha 9 blockade suppresses lymphatic valve formation and promotes transplant survival
topic Cornea
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096415/
https://www.ncbi.nlm.nih.gov/pubmed/27806381
http://dx.doi.org/10.1167/iovs.16-20130
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