iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity
| Autor: | Natsumi Higashi, Yoshikazu Hayashi, Akitsu Hotta, Kosuke Fujio, Hitoshi Takizawa, Koji Eto, Markus G. Manz, Marina Akasaka, Charlotte Flahou, Huaigeng Xu, Takuya Matsumoto, Sou Nakamura, Daisuke Suzuki, Norihide Yoshikawa, Naoshi Sugimoto, Ieva Stirblyte, Akira Sawaguchi |
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| Přispěvatelé: | University of Zurich, Eto, Koji |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine 1303 Biochemistry Lymphocyte Activation Biochemistry megakaryocyte 1309 Developmental Biology 1307 Cell Biology Gene Knockout Techniques Mice 0302 clinical medicine Cytotoxic T cell Platelet Induced pluripotent stem cell imMKCL lcsh:QH301-705.5 Mice Knockout platelet lcsh:R5-920 iPSC refractoriness MSTRG mice Cell Differentiation Killer Cells Natural medicine.anatomical_structure IL-15 lcsh:Medicine (General) Blood Platelets Induced Pluripotent Stem Cells regenerative medicine 610 Medicine & health Human leukocyte antigen Biology Article Natural killer cell 03 medical and health sciences Human leukocyte antigen class I 1311 Genetics Immunity Genetics medicine Animals Humans Histocompatibility Antigens Class I HLA class I Cell Biology natural killer cell Platelet transfusion refractoriness 030104 developmental biology lcsh:Biology (General) Immunology 10032 Clinic for Oncology and Hematology platelet transfusion beta 2-Microglobulin 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cell Reports, Vol 14, Iss 1, Pp 49-59 (2020) Stem Cell Reports |
| DOI: | 10.5167/uzh-180152 |
| Popis: | Summary The ex vivo production of platelets depleted of human leukocyte antigen class I (HLA-I) could serve as a universal measure to overcome platelet transfusion refractoriness caused by HLA-I incompatibility. Here, we developed human induced pluripotent cell-derived HLA-I-deficient platelets (HLA-KO iPLATs) in a clinically applicable imMKCL system by genetic manipulation and assessed their immunogenic properties including natural killer (NK) cells, which reject HLA-I downregulated cells. HLA-KO iPLATs were deficient for all HLA-I but did not elicit a cytotoxic response by NK cells in vitro and showed circulation equal to wild-type iPLATs upon transfusion in our newly established Hu-NK-MSTRG mice reconstituted with human NK cells. Additionally, HLA-KO iPLATs successfully circulated in an alloimmune platelet transfusion refractoriness model of Hu-NK-MISTRG mice. Mechanistically, the lack of NK cell-activating ligands on platelets may be responsible for evading the NK cell response. This study revealed the unique non-immunogenic property of platelets and provides a proof of concept for the clinical application of HLA-KO iPLATs. Graphical Abstract Highlights • Clinically applicable iPSC-derived HLA class I knockout platelets (HLA-KO iPLATs) • HLA-KO iPLATs do not elicit NK cell activation in vitro • HLA-KO iPLATs circulate comparably with wild type in human NK cell-reconstituted mice • HLA-KO iPLATs circulate competently in alloimmune PTR model mice T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. |
| Databáze: | OpenAIRE |
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