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Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival
CDK9 (Cyclin-dependent kinase 9)/Cyclin T1/RNA polymerase II pathway has been demonstrated to promote the development of several inflammatory diseases, such as arthritis or atherosclerosis, however, its roles in allotransplantation rejection have not been addressed. Here, we found that CDK9/Cyclin T...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041884/ https://www.ncbi.nlm.nih.gov/pubmed/27102157 http://dx.doi.org/10.18632/oncotarget.8804 |
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author | Zhan, Yang Han, Yeming Sun, Hukui Liang, Ting Zhang, Chao Song, Jing Hou, Guihua |
author_facet | Zhan, Yang Han, Yeming Sun, Hukui Liang, Ting Zhang, Chao Song, Jing Hou, Guihua |
author_sort | Zhan, Yang |
collection | PubMed |
description | CDK9 (Cyclin-dependent kinase 9)/Cyclin T1/RNA polymerase II pathway has been demonstrated to promote the development of several inflammatory diseases, such as arthritis or atherosclerosis, however, its roles in allotransplantation rejection have not been addressed. Here, we found that CDK9/Cyclin T1 were apparently up-regulated in the allogeneic group, which was positively correlated with allograft damage. CDK9 was inhibited obviously in naive splenic CD4(+) T cells treated 6 h with 3 μM PHA767491 (a CDK9 inhibitor), and adoptive transfer of these CD4(+) T cells into allografted SCID mice resulted in prolonged survival compared with the group without PHA767491 pretreated. Decelerated rejection was correlated with enhanced IL-4 and IL-10 production and with decreased IFN-γ production by alloreactive T cells. More interestingly, we found that CDK9(42), not CDK9(55), was high expressed in allorejection group, which could be prominently dampened with PHA767491 treatment. The expression of CDK9(42) was consistent with its downstream molecule RNA polymerase II. Altogether, our findings revealed the crucial role of CDK9/Cyclin T1/Pol II pathway in promoting allorejection at multiple levels and may provide a new approach for transplantation tolerance induction through targeting CDK9. |
format | Online Article Text |
id | pubmed-5041884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50418842016-10-10 Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival Zhan, Yang Han, Yeming Sun, Hukui Liang, Ting Zhang, Chao Song, Jing Hou, Guihua Oncotarget Research Paper: Immunology CDK9 (Cyclin-dependent kinase 9)/Cyclin T1/RNA polymerase II pathway has been demonstrated to promote the development of several inflammatory diseases, such as arthritis or atherosclerosis, however, its roles in allotransplantation rejection have not been addressed. Here, we found that CDK9/Cyclin T1 were apparently up-regulated in the allogeneic group, which was positively correlated with allograft damage. CDK9 was inhibited obviously in naive splenic CD4(+) T cells treated 6 h with 3 μM PHA767491 (a CDK9 inhibitor), and adoptive transfer of these CD4(+) T cells into allografted SCID mice resulted in prolonged survival compared with the group without PHA767491 pretreated. Decelerated rejection was correlated with enhanced IL-4 and IL-10 production and with decreased IFN-γ production by alloreactive T cells. More interestingly, we found that CDK9(42), not CDK9(55), was high expressed in allorejection group, which could be prominently dampened with PHA767491 treatment. The expression of CDK9(42) was consistent with its downstream molecule RNA polymerase II. Altogether, our findings revealed the crucial role of CDK9/Cyclin T1/Pol II pathway in promoting allorejection at multiple levels and may provide a new approach for transplantation tolerance induction through targeting CDK9. Impact Journals LLC 2016-04-18 /pmc/articles/PMC5041884/ /pubmed/27102157 http://dx.doi.org/10.18632/oncotarget.8804 Text en Copyright: © 2016 Zhan et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper: Immunology Zhan, Yang Han, Yeming Sun, Hukui Liang, Ting Zhang, Chao Song, Jing Hou, Guihua Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival |
title | Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival |
title_full | Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival |
title_fullStr | Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival |
title_full_unstemmed | Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival |
title_short | Down-regulating cyclin-dependent kinase 9 of alloreactive CD4(+) T cells prolongs allograft survival |
title_sort | down-regulating cyclin-dependent kinase 9 of alloreactive cd4(+) t cells prolongs allograft survival |
topic | Research Paper: Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041884/ https://www.ncbi.nlm.nih.gov/pubmed/27102157 http://dx.doi.org/10.18632/oncotarget.8804 |
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