PMID- 26506955 OWN - NLM STAT- MEDLINE DCOM- 20160519 LR - 20231213 IS - 0717-6287 (Electronic) IS - 0716-9760 (Print) IS - 0716-9760 (Linking) VI - 48 DP - 2015 Oct 27 TI - Functional disruption of human leukocyte antigen II in human embryonic stem cell. PG - 59 LID - 10.1186/s40659-015-0051-6 [doi] LID - 59 AB - 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. FAU - Chen, Haide AU - Chen H AD - College of Animal Science, Zhejiang University, Hangzhou, 310058, People's Republic of China. Hyde@zju.edu.cn. AD - Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China. Hyde@zju.edu.cn. FAU - Li, Yang AU - Li Y AD - College of Animal Science, Zhejiang University, Hangzhou, 310058, People's Republic of China. Younglee@zju.edu.cn. AD - Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China. Younglee@zju.edu.cn. FAU - Lin, Xijuan AU - Lin X AD - College of Animal Science, Zhejiang University, Hangzhou, 310058, People's Republic of China. 11217009@zju.edu.cn. AD - Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China. 11217009@zju.edu.cn. FAU - Cui, Di AU - Cui D AD - College of Animal Science, Zhejiang University, Hangzhou, 310058, People's Republic of China. 21217007@zju.edu.cn. AD - Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China. 21217007@zju.edu.cn. FAU - Cui, Chun AU - Cui C AD - Wuxi Medical School, Jiangnan University, Wuxi, 214122, People's Republic of China. Cuichun@jiangnan.edu.cn. FAU - Li, Hui AU - Li H AD - Xiangtan Center Hospital, Hunan, 411100, People's Republic of China. Lihui_1973@126.com. FAU - Xiao, Lei AU - Xiao L AD - College of Animal Science, Zhejiang University, Hangzhou, 310058, People's Republic of China. Leixiao@zju.edu.cn. AD - Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China. Leixiao@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151027 PL - England TA - Biol Res JT - Biological research JID - 9308271 RN - 0 (Antigens, CD) RN - 0 (B7-2 Antigen) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Immunoglobulins) RN - 0 (MHC class II transactivator protein) RN - 0 (Membrane Glycoproteins) RN - 0 (Nuclear Proteins) RN - 0 (Trans-Activators) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.1.- (Deoxyribonucleases) SB - IM MH - Animals MH - Antigen-Presenting Cells/metabolism MH - Antigens, CD/metabolism MH - B7-2 Antigen/metabolism MH - Cell Differentiation/*genetics MH - Cell Self Renewal MH - Dendritic Cells/metabolism MH - Deoxyribonucleases/classification/*metabolism MH - Embryoid Bodies/metabolism MH - Fibroblasts/metabolism MH - *Gene Deletion MH - Histocompatibility Antigens Class II/genetics MH - Human Embryonic Stem Cells/*metabolism MH - Humans MH - Immunoglobulins/metabolism MH - Immunohistochemistry MH - Interferon-gamma/metabolism MH - Karyotype MH - Membrane Glycoproteins/metabolism MH - Mice MH - Mice, SCID MH - Nuclear Proteins/*genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Teratoma MH - Trans-Activators/*genetics MH - Tumor Cells, Cultured MH - CD83 Antigen PMC - PMC4624597 EDAT- 2015/10/29 06:00 MHDA- 2016/05/20 06:00 PMCR- 2015/10/27 CRDT- 2015/10/29 06:00 PHST- 2015/05/27 00:00 [received] PHST- 2015/10/20 00:00 [accepted] PHST- 2015/10/29 06:00 [entrez] PHST- 2015/10/29 06:00 [pubmed] PHST- 2016/05/20 06:00 [medline] PHST- 2015/10/27 00:00 [pmc-release] AID - 10.1186/s40659-015-0051-6 [pii] AID - 51 [pii] AID - 10.1186/s40659-015-0051-6 [doi] PST - epublish SO - Biol Res. 2015 Oct 27;48:59. doi: 10.1186/s40659-015-0051-6.