期刊
BIOLOGICAL RESEARCH
卷 48, 期 -, 页码 -出版社
SOC BIOLGIA CHILE
DOI: 10.1186/s40659-015-0051-6
关键词
hESCs; CIITA; TALENs; Immune rejection
类别
资金
- Ministry of Agriculture [2014ZX0801-011B]
- National Natural Science Foundation of China [31271577]
- Zhejiang Provincial Natural Science Foundation of China [LY13C120001]
- Novel Agricultural Variety Breeding Project of Zhejiang Province [2012C12906-8]
- Ministry of Science and Technology of China [2011CB965101, 2012AA020503, 2012CB966601]
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. Allograft 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-gamma inducible expression of HLA II. Conclusion: We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-gamma 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.
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