Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.

The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF)...

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Autores principales: Toshiaki Nakano, Chia-Yun Lai, Shigeru Goto, Li-Wen Hsu, Seiji Kawamoto, Kazuhisa Ono, Kuang-Den Chen, Chih-Che Lin, King-Wah Chiu, Chih-Chi Wang, Yu-Fan Cheng, Chao-Long Chen
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:fde646e77df14ed5ba75bbe3687301112021-11-18T07:18:37ZImmunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.1932-620310.1371/journal.pone.0037202https://doaj.org/article/fde646e77df14ed5ba75bbe3687301112012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22615941/?tool=EBIhttps://doaj.org/toc/1932-6203The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3+ Tregs, γδ T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-β1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow-derived mast cells (BMMCs) co-cultured with naïve splenocytes or primary hepatocytes significantly increased the population of splenic γδ T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient.Toshiaki NakanoChia-Yun LaiShigeru GotoLi-Wen HsuSeiji KawamotoKazuhisa OnoKuang-Den ChenChih-Che LinKing-Wah ChiuChih-Chi WangYu-Fan ChengChao-Long ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37202 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Toshiaki Nakano
Chia-Yun Lai
Shigeru Goto
Li-Wen Hsu
Seiji Kawamoto
Kazuhisa Ono
Kuang-Den Chen
Chih-Che Lin
King-Wah Chiu
Chih-Chi Wang
Yu-Fan Cheng
Chao-Long Chen
Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
description The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3+ Tregs, γδ T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-β1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow-derived mast cells (BMMCs) co-cultured with naïve splenocytes or primary hepatocytes significantly increased the population of splenic γδ T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient.
format article
author Toshiaki Nakano
Chia-Yun Lai
Shigeru Goto
Li-Wen Hsu
Seiji Kawamoto
Kazuhisa Ono
Kuang-Den Chen
Chih-Che Lin
King-Wah Chiu
Chih-Chi Wang
Yu-Fan Cheng
Chao-Long Chen
author_facet Toshiaki Nakano
Chia-Yun Lai
Shigeru Goto
Li-Wen Hsu
Seiji Kawamoto
Kazuhisa Ono
Kuang-Den Chen
Chih-Che Lin
King-Wah Chiu
Chih-Chi Wang
Yu-Fan Cheng
Chao-Long Chen
author_sort Toshiaki Nakano
title Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
title_short Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
title_full Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
title_fullStr Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
title_full_unstemmed Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
title_sort immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/fde646e77df14ed5ba75bbe368730111
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