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Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models

Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi...

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Autores principales: Mori, Akihiro, Murata, Soichiro, Tashiro, Nao, Tadokoro, Tomomi, Okamoto, Satoshi, Otsuka, Ryo, Wada, Haruka, Murata, Tomoki, Takahashi, Takeshi, Seino, Ken-ichiro, Taniguchi, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927063/
https://www.ncbi.nlm.nih.gov/pubmed/33672150
http://dx.doi.org/10.3390/cells10020476
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author Mori, Akihiro
Murata, Soichiro
Tashiro, Nao
Tadokoro, Tomomi
Okamoto, Satoshi
Otsuka, Ryo
Wada, Haruka
Murata, Tomoki
Takahashi, Takeshi
Seino, Ken-ichiro
Taniguchi, Hideki
author_facet Mori, Akihiro
Murata, Soichiro
Tashiro, Nao
Tadokoro, Tomomi
Okamoto, Satoshi
Otsuka, Ryo
Wada, Haruka
Murata, Tomoki
Takahashi, Takeshi
Seino, Ken-ichiro
Taniguchi, Hideki
author_sort Mori, Akihiro
collection PubMed
description Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice. After the transplantation of HLA-A2 human hematopoietic stem cells into NOG-HLA-A2Tg, we succeeded in achieving alloimmune responses after the HLA-mismatched human-induced pluripotent stem cell (hiPSC)-derived liver-like tissue transplantation. This immune response was inhibited by administering tacrolimus. In this model, we reproduced allograft rejection after the human iPSC-derived liver-like tissue transplantation. Human tissue transplantation on the humanized mouse liver surface is a good model that can predict T-cell-mediated cellular rejection that may occur when organ transplantation is performed.
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spelling pubmed-79270632021-03-04 Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models Mori, Akihiro Murata, Soichiro Tashiro, Nao Tadokoro, Tomomi Okamoto, Satoshi Otsuka, Ryo Wada, Haruka Murata, Tomoki Takahashi, Takeshi Seino, Ken-ichiro Taniguchi, Hideki Cells Article Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice. After the transplantation of HLA-A2 human hematopoietic stem cells into NOG-HLA-A2Tg, we succeeded in achieving alloimmune responses after the HLA-mismatched human-induced pluripotent stem cell (hiPSC)-derived liver-like tissue transplantation. This immune response was inhibited by administering tacrolimus. In this model, we reproduced allograft rejection after the human iPSC-derived liver-like tissue transplantation. Human tissue transplantation on the humanized mouse liver surface is a good model that can predict T-cell-mediated cellular rejection that may occur when organ transplantation is performed. MDPI 2021-02-23 /pmc/articles/PMC7927063/ /pubmed/33672150 http://dx.doi.org/10.3390/cells10020476 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mori, Akihiro
Murata, Soichiro
Tashiro, Nao
Tadokoro, Tomomi
Okamoto, Satoshi
Otsuka, Ryo
Wada, Haruka
Murata, Tomoki
Takahashi, Takeshi
Seino, Ken-ichiro
Taniguchi, Hideki
Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models
title Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models
title_full Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models
title_fullStr Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models
title_full_unstemmed Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models
title_short Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models
title_sort establishment of human leukocyte antigen-mismatched immune responses after transplantation of human liver bud in humanized mouse models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927063/
https://www.ncbi.nlm.nih.gov/pubmed/33672150
http://dx.doi.org/10.3390/cells10020476
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