Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance

Article


Smyth, L., Meader, Lucy, Xiao, Fang, Woodward, Martin, Brady, Hugh J., Lechler, Robert and Lombardi, Giovanna 2017. Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance. Clinical and Experimental Immunology. 188 (2), pp. 219-225. https://doi.org/10.1111/cei.12931
AuthorsSmyth, L., Meader, Lucy, Xiao, Fang, Woodward, Martin, Brady, Hugh J., Lechler, Robert and Lombardi, Giovanna
Abstract

Anti-apoptotic genes including those of the Bcl-2 family have been shown to have dual functionality in as much as they inhibit cell death but also regulate inflammation. Several anti-apoptotic molecules have been associated with endothelial cell (EC) survival following transplantation however their exact role has yet to be elucidated in respect to controlling inflammation. In this study we created mice expressing murine A1 (Bfl-1), a Bcl-2 family member, under the control of the human ICAM-2 promoter. Constitutive expression of A1 in murine vascular ECs conferred protection from cell death induced by the pro-inflammatory cytokine TNF-α. Importantly, in a mouse model of heart allograft transplantation, expression of A1 in vascular endothelium increased survival in the absence of CD8+ T cells. Better graft outcome in mice receiving an A1 transgenic heart correlated with a reduced immune infiltration, which maybe related to increased EC survival and reduced expression of adhesion molecules on ECs. In conclusion, constitutive expression of the anti-apoptotic molecule Bfl1 (A1) in murine vascular ECs leads to prolonged allograft survival due to modifying inflammation.

Keywordsendothelial; anti-apoptotic
JournalClinical and Experimental Immunology
Journal citation188 (2), pp. 219-225
ISSN0009-9104
1365-2249
Year2017
PublisherWiley for British Society for Immunology
Accepted author manuscript
License
Digital Object Identifier (DOI)https://doi.org/10.1111/cei.12931
Web address (URL)http://doi.org/10.1111/cei.12931
Publication dates
Print24 Jan 2017
Publication process dates
Deposited02 Mar 2017
Accepted06 Jan 2017
FunderBritish Heart Foundation
National Institute for Health Research (NIHR)
Guy's and Thomas’ NHS Foundation Trust
King's College London
British Heart Foundation
National Institute for Health Research
Guy's and St Thomas' NHS Foundation Trust
King's College London
Copyright informationThis is the peer reviewed version of the following article: Smyth, L. A., Meader, L., Xiao, F., Woodward, M., Brady, H. J., Lechler, R. and Lombardi, G. (2017), Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance, Clinical and Experimental Immunology, which has been published in final form at doi:10.1111/cei.12931. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
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