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Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity

Ischemic preconditioning (IPC) protects organs from ischemia reperfusion injury (IRI) through unknown mechanisms. Effector T cell populations have been implicated in the pathogenesis of IRI, and T regulatory cells (Treg) have become a putative therapeutic target, with suggested involvement in IPC. W...

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Autores principales: Devey, Luke R., Richards, James A., O’Connor, Richard A., Borthwick, Gary, Clay, Spike, Howie, A. Forbes, Wigmore, Stephen J., Anderton, Stephen M., Howie, Sarah E. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504160/
https://www.ncbi.nlm.nih.gov/pubmed/23185394
http://dx.doi.org/10.1371/journal.pone.0049647
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author Devey, Luke R.
Richards, James A.
O’Connor, Richard A.
Borthwick, Gary
Clay, Spike
Howie, A. Forbes
Wigmore, Stephen J.
Anderton, Stephen M.
Howie, Sarah E. M.
author_facet Devey, Luke R.
Richards, James A.
O’Connor, Richard A.
Borthwick, Gary
Clay, Spike
Howie, A. Forbes
Wigmore, Stephen J.
Anderton, Stephen M.
Howie, Sarah E. M.
author_sort Devey, Luke R.
collection PubMed
description Ischemic preconditioning (IPC) protects organs from ischemia reperfusion injury (IRI) through unknown mechanisms. Effector T cell populations have been implicated in the pathogenesis of IRI, and T regulatory cells (Treg) have become a putative therapeutic target, with suggested involvement in IPC. We explored the role of Treg in hepatic IRI and IPC in detail. IPC significantly reduced injury following ischemia reperfusion insults. Treg were mobilized rapidly to the circulation and liver after IRI, but IPC did not further increase Treg numbers, nor was it associated with modulation of circulating pro-inflammatory chemokine or cytokine profiles. We used two techniques to deplete Treg from mice prior to IRI. Neither Treg depleted FoxP3.LuciDTR mice, nor wildtyoe mice depleted of Tregs with PC61, were more susceptible to IRI compared with controls. Despite successful enrichment of Treg in the liver, by adoptive transfer of both iTreg and nTreg or by in vivo expansion of Treg with IL-2/anti-IL-2 complexes, no protection against IRI was observed.We have explored the role of Treg in IRI and IPC using a variety of techniques to deplete and enrich them within both the liver and systemically. This work represents an important negative finding that Treg are not implicated in IPC and are unlikely to have translational potential in hepatic IRI.
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spelling pubmed-35041602012-11-26 Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity Devey, Luke R. Richards, James A. O’Connor, Richard A. Borthwick, Gary Clay, Spike Howie, A. Forbes Wigmore, Stephen J. Anderton, Stephen M. Howie, Sarah E. M. PLoS One Research Article Ischemic preconditioning (IPC) protects organs from ischemia reperfusion injury (IRI) through unknown mechanisms. Effector T cell populations have been implicated in the pathogenesis of IRI, and T regulatory cells (Treg) have become a putative therapeutic target, with suggested involvement in IPC. We explored the role of Treg in hepatic IRI and IPC in detail. IPC significantly reduced injury following ischemia reperfusion insults. Treg were mobilized rapidly to the circulation and liver after IRI, but IPC did not further increase Treg numbers, nor was it associated with modulation of circulating pro-inflammatory chemokine or cytokine profiles. We used two techniques to deplete Treg from mice prior to IRI. Neither Treg depleted FoxP3.LuciDTR mice, nor wildtyoe mice depleted of Tregs with PC61, were more susceptible to IRI compared with controls. Despite successful enrichment of Treg in the liver, by adoptive transfer of both iTreg and nTreg or by in vivo expansion of Treg with IL-2/anti-IL-2 complexes, no protection against IRI was observed.We have explored the role of Treg in IRI and IPC using a variety of techniques to deplete and enrich them within both the liver and systemically. This work represents an important negative finding that Treg are not implicated in IPC and are unlikely to have translational potential in hepatic IRI. Public Library of Science 2012-11-21 /pmc/articles/PMC3504160/ /pubmed/23185394 http://dx.doi.org/10.1371/journal.pone.0049647 Text en © 2012 Devey et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Devey, Luke R.
Richards, James A.
O’Connor, Richard A.
Borthwick, Gary
Clay, Spike
Howie, A. Forbes
Wigmore, Stephen J.
Anderton, Stephen M.
Howie, Sarah E. M.
Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity
title Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity
title_full Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity
title_fullStr Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity
title_full_unstemmed Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity
title_short Ischemic Preconditioning in the Liver Is Independent of Regulatory T Cell Activity
title_sort ischemic preconditioning in the liver is independent of regulatory t cell activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504160/
https://www.ncbi.nlm.nih.gov/pubmed/23185394
http://dx.doi.org/10.1371/journal.pone.0049647
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