Functional disruption of human leukocyte antigen II in human embryonic stem cell
Biol. Res
; 48: 1-9, 2015. ilus, graf
Artigo
em Inglês
| 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.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Proteínas Nucleares
/
Diferenciação Celular
/
Transativadores
/
Deleção de Genes
/
Desoxirribonucleases
/
Células-Tronco Embrionárias Humanas
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Biol. Res
Assunto da revista:
Biologia
Ano de publicação:
2015
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
Jiangnan University/CN
/
Xiangtan Center Hospital/CN
/
Zhejiang University/CN