Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts.
Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110δ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032892&type=printable |
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| author | Huijun Ying Hongmei Fu Marlene L Rose Ann M McCormack Padmini Sarathchandra Klaus Okkenhaug Federica M Marelli-Berg |
| author_facet | Huijun Ying Hongmei Fu Marlene L Rose Ann M McCormack Padmini Sarathchandra Klaus Okkenhaug Federica M Marelli-Berg |
| author_sort | Huijun Ying |
| collection | DOAJ |
| description | Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110δ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110δ on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110δ activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110δ pharmacologic inactivation is effective when initiated after transplantation. Targeting p110δ activity might be a viable strategy for the treatment of heart chronic rejection in humans. |
| format | Article |
| id | doaj-art-65dd6dbf09034d55ac309e0df66ebb50 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-65dd6dbf09034d55ac309e0df66ebb502025-08-20T03:26:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3289210.1371/journal.pone.0032892Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts.Huijun YingHongmei FuMarlene L RoseAnn M McCormackPadmini SarathchandraKlaus OkkenhaugFederica M Marelli-BergChronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110δ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110δ on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110δ activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110δ pharmacologic inactivation is effective when initiated after transplantation. Targeting p110δ activity might be a viable strategy for the treatment of heart chronic rejection in humans.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032892&type=printable |
| spellingShingle | Huijun Ying Hongmei Fu Marlene L Rose Ann M McCormack Padmini Sarathchandra Klaus Okkenhaug Federica M Marelli-Berg Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts. PLoS ONE |
| title | Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts. |
| title_full | Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts. |
| title_fullStr | Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts. |
| title_full_unstemmed | Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts. |
| title_short | Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts. |
| title_sort | genetic or pharmaceutical blockade of phosphoinositide 3 kinase p110δ prevents chronic rejection of heart allografts |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0032892&type=printable |
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