Functional disruption of human leukocyte antigen II in human embryonic stem cell
Biol. Res
; 48: 1-9, 2015. ilus, graf
Article
em En
| LILACS
| ID: biblio-950823
Biblioteca responsável:
CL1.1
ABSTRACT
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.Palavras-chave
Texto completo:
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Índice:
LILACS
Assunto principal:
Proteínas Nucleares
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Diferenciação Celular
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Transativadores
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Deleção de Genes
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Desoxirribonucleases
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Células-Tronco Embrionárias Humanas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biol. Res
Assunto da revista:
BIOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article