Differential role of natural killer group 2D in recognition and cytotoxicity of hepatocyte-like cells derived from embryonic stem cells and induced pluripotent stem cells
| Autor: | Justin Arredondo‐Guerrero, Martha Castro, Renata M. Martin, Sheri M. Krams, Steven Schaffert, Carlos O. Esquivel, X. Qu, Danielle W. Dillard, Olivia M. Martinez, Trinidad Cisneros |
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| Rok vydání: | 2019 |
| Předmět: |
Cytotoxicity
Immunologic Male Cell Transplantation Induced Pluripotent Stem Cells Cell Mice Transgenic Mice SCID 030230 surgery Ligands Regenerative medicine Article Mice 03 medical and health sciences 0302 clinical medicine Mice Inbred NOD MHC class I medicine Animals Humans Immunology and Allergy Pharmacology (medical) Induced pluripotent stem cell Embryonic Stem Cells Mice Knockout Transplantation Isografts biology business.industry Gene Expression Profiling Cell Differentiation Allografts NKG2D Embryonic stem cell Cell biology Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K Models Animal Hepatocytes biology.protein Female Stem cell business |
| Zdroj: | Am J Transplant |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/ajt.15217 |
| Popis: | Stem cell-based approaches have the potential to address the organ shortage in transplantation. Whereas both embryonic stem cells and induced pluripotent stem cells have been utilized as cellular sources for differentiation and lineage specification, their relative ability to be recognized by immune effector cells is unclear. We determined the expression of immune recognition molecules on hepatocyte-like cells (HLC) generated from murine embryonic stem cells and induced pluripotent stem cells, compared to adult hepatocytes, and we evaluated the impact on recognition by natural killer (NK) cells. We report that HLC lack MHC class I expression, and that embryonic stem cell-derived HLC have higher expression of the NK cell activating ligands Rae1, H60, and Mult1 than induced pluripotent stem cell-derived HLC and adult hepatocytes. Moreover, the lack of MHC class I renders embryonic stem cell-derived HLC, and induced pluripotent stem cell-derived HLC, susceptible to killing by syngeneic and allogeneic NK cells. Both embryonic stem cell-derived HLC, and induced pluripotent stem cell-derived HLC, are killed by NK cells at higher levels than adult hepatocytes. Finally, we demonstrate that the NK cell activation receptor, NKG2D, plays a key role in NK cell cytotoxicity of embryonic stem cell-derived HLC, but not induced pluripotent stem cell-derived HLC. |
| Databáze: | OpenAIRE |
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