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Functional disruption of human leukocyte antigen II in human embryonic stem cell
- Source :
- Biological Research, Vol 48, Iss 0, Pp 1-9 (2015), Biological Research v.48 2015, SciELO Chile, CONICYT Chile, instacron:CONICYT, Biological Research, Biological Research, Volume: 48, Pages: 1-9, Published: 2015
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
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. 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-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. Electronic supplementary material The online version of this article (doi:10.1186/s40659-015-0051-6) contains supplementary material, which is available to authorized users.
- Subjects :
- Cellular immunity
Cellular differentiation
Human Embryonic Stem Cells
Mice, SCID
Embryoid body
Mice
Tumor Cells, Cultured
Cell Self Renewal
lcsh:QH301-705.5
reproductive and urinary physiology
Medicine(all)
Deoxyribonucleases
Membrane Glycoproteins
Agricultural and Biological Sciences(all)
Reverse Transcriptase Polymerase Chain Reaction
Teratoma
CIITA
Nuclear Proteins
Cell Differentiation
Immunohistochemistry
Cell biology
TALENs
embryonic structures
biological phenomena, cell phenomena, and immunity
Research Article
Immune rejection
Karyotype
Antigen-Presenting Cells
Immunoglobulins
chemical and pharmacologic phenomena
Human leukocyte antigen
Biology
Real-Time Polymerase Chain Reaction
Interferon-gamma
Antigens, CD
Animals
Humans
Antigen-presenting cell
Embryoid Bodies
CD86
Biochemistry, Genetics and Molecular Biology(all)
Histocompatibility Antigens Class II
Dendritic Cells
Fibroblasts
equipment and supplies
Embryonic stem cell
lcsh:Biology (General)
hESCs
Immunology
Trans-Activators
B7-2 Antigen
Gene Deletion
Subjects
Details
- ISSN :
- 07176287
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Biological Research
- Accession number :
- edsair.doi.dedup.....0bcef82136ac4ecceba253235eaeb350