Functional disruption of human leukocyte antigen II in human embryonic stem cell

BACKGROUND: Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exac...

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Autores principales:	Chen,Haide, Li,Yang, Lin,Xijuan, Cui,Di, Cui,Chun, Li,Hui, Xiao,Lei
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2015
Materias:	hESCs CIITA TALENs Immune rejection
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100059
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spelling	oai:scielo:S0716-976020150001000592016-02-16Functional disruption of human leukocyte antigen II in human embryonic stem cellChen,HaideLi,YangLin,XijuanCui,DiCui,ChunLi,HuiXiao,Lei hESCs CIITA TALENs Immune rejection BACKGROUND: Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exact same type of cells derived from hESCs. Allo-graft immune rejection is one of the obstacles for hESCs-based clinical applications. Human leukocyte antigen (HLA) II leads to CD4+ T cells-mediated allograft rejection. Hence, we focus on optimizing hESCs for clinic application through gene modification RESULTS: Transcription activator-like effector nucleases (TALENs) were used to target MHC class II transactivator (CIITA) in hESCs efficiently. CIITA-/-hESCs did not show any difference in the differentiation potential and self-renewal capacity. Dendritic cells (DCs) derived from CIITA-/-hESCs expressed CD83 and CD86 but without the constitutive HLA II. Fibroblasts derived from CIITA-/-hESCs were powerless in IFN-γ inducible expression of HLA II CONCLUSION: We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-γ inducible expression of HLA II genes. CIITA-/-hESCs can differentiate into tissue cells with non-HLA II expression. It's promising that CIITA-/-hESCs-derived cells could be used in cell therapy (e.g., T cells and DCs) and escape the attack of receptors' CD4+ T cells, which are the main effector cells of cellular immunity in allograftinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.48 20152015-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100059en10.1186/S40659-015-0051-6
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	hESCs CIITA TALENs Immune rejection
spellingShingle	hESCs CIITA TALENs Immune rejection Chen,Haide Li,Yang Lin,Xijuan Cui,Di Cui,Chun Li,Hui Xiao,Lei Functional disruption of human leukocyte antigen II in human embryonic stem cell
description	BACKGROUND: Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exact same type of cells derived from hESCs. Allo-graft immune rejection is one of the obstacles for hESCs-based clinical applications. Human leukocyte antigen (HLA) II leads to CD4+ T cells-mediated allograft rejection. Hence, we focus on optimizing hESCs for clinic application through gene modification RESULTS: Transcription activator-like effector nucleases (TALENs) were used to target MHC class II transactivator (CIITA) in hESCs efficiently. CIITA-/-hESCs did not show any difference in the differentiation potential and self-renewal capacity. Dendritic cells (DCs) derived from CIITA-/-hESCs expressed CD83 and CD86 but without the constitutive HLA II. Fibroblasts derived from CIITA-/-hESCs were powerless in IFN-γ inducible expression of HLA II CONCLUSION: We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-γ inducible expression of HLA II genes. CIITA-/-hESCs can differentiate into tissue cells with non-HLA II expression. It's promising that CIITA-/-hESCs-derived cells could be used in cell therapy (e.g., T cells and DCs) and escape the attack of receptors' CD4+ T cells, which are the main effector cells of cellular immunity in allograft
author	Chen,Haide Li,Yang Lin,Xijuan Cui,Di Cui,Chun Li,Hui Xiao,Lei
author_facet	Chen,Haide Li,Yang Lin,Xijuan Cui,Di Cui,Chun Li,Hui Xiao,Lei
author_sort	Chen,Haide
title	Functional disruption of human leukocyte antigen II in human embryonic stem cell
title_short	Functional disruption of human leukocyte antigen II in human embryonic stem cell
title_full	Functional disruption of human leukocyte antigen II in human embryonic stem cell
title_fullStr	Functional disruption of human leukocyte antigen II in human embryonic stem cell
title_full_unstemmed	Functional disruption of human leukocyte antigen II in human embryonic stem cell
title_sort	functional disruption of human leukocyte antigen ii in human embryonic stem cell
publisher	Sociedad de Biología de Chile
publishDate	2015
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100059
work_keys_str_mv	AT chenhaide functionaldisruptionofhumanleukocyteantigeniiinhumanembryonicstemcell AT liyang functionaldisruptionofhumanleukocyteantigeniiinhumanembryonicstemcell AT linxijuan functionaldisruptionofhumanleukocyteantigeniiinhumanembryonicstemcell AT cuidi functionaldisruptionofhumanleukocyteantigeniiinhumanembryonicstemcell AT cuichun functionaldisruptionofhumanleukocyteantigeniiinhumanembryonicstemcell AT lihui functionaldisruptionofhumanleukocyteantigeniiinhumanembryonicstemcell AT xiaolei functionaldisruptionofhumanleukocyteantigeniiinhumanembryonicstemcell
_version_	1718441542838910976

Functional disruption of human leukocyte antigen II in human embryonic stem cell

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