RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice

Abstract Calcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delive...

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Autores principales:	Hirofumi Noguchi, Koji Sugimoto, Chika Miyagi-Shiohira, Yoshiki Nakashima, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0a1298d24d44d60b856dbc18ce5f181
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spelling	oai:doaj.org-article:d0a1298d24d44d60b856dbc18ce5f1812021-12-02T11:41:21ZRCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice10.1038/s41598-017-02934-32045-2322https://doaj.org/article/d0a1298d24d44d60b856dbc18ce5f1812017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02934-3https://doaj.org/toc/2045-2322Abstract Calcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide (11R-VIVIT) selectively interferes with calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase and provides immunosuppression for fully mismatched islet allografts in mice. However, our recent study showed that 11R-VIVIT affected cell viability in vitro when it was used at higher concentration because of the VIVIT sequence. The aim of this study is to develop a safer NFAT inhibitor (RCAN-11R) that does not affect cell viability, and which is less toxic than calcineurin inhibitors. The minimal sequence of the protein family of regulators of calcineurin (RCAN) that is responsible for the inhibition of calcineurin-NFAT signaling was recently characterized. The peptide could selectively interfere with the calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase, similar to 11R-VIVIT. RCAN-11R did not affect cell viability when it was used at a higher concentration than the toxic concentration of 11R-VIVIT. RCAN-11R could therefore be useful as a therapeutic agent that is less toxic than current drugs or 11R-VIVIT.Hirofumi NoguchiKoji SugimotoChika Miyagi-ShiohiraYoshiki NakashimaNaoya KobayashiIssei SaitohMasami WatanabeYasufumi NoguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hirofumi Noguchi Koji Sugimoto Chika Miyagi-Shiohira Yoshiki Nakashima Naoya Kobayashi Issei Saitoh Masami Watanabe Yasufumi Noguchi RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice
description	Abstract Calcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide (11R-VIVIT) selectively interferes with calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase and provides immunosuppression for fully mismatched islet allografts in mice. However, our recent study showed that 11R-VIVIT affected cell viability in vitro when it was used at higher concentration because of the VIVIT sequence. The aim of this study is to develop a safer NFAT inhibitor (RCAN-11R) that does not affect cell viability, and which is less toxic than calcineurin inhibitors. The minimal sequence of the protein family of regulators of calcineurin (RCAN) that is responsible for the inhibition of calcineurin-NFAT signaling was recently characterized. The peptide could selectively interfere with the calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase, similar to 11R-VIVIT. RCAN-11R did not affect cell viability when it was used at a higher concentration than the toxic concentration of 11R-VIVIT. RCAN-11R could therefore be useful as a therapeutic agent that is less toxic than current drugs or 11R-VIVIT.
format	article
author	Hirofumi Noguchi Koji Sugimoto Chika Miyagi-Shiohira Yoshiki Nakashima Naoya Kobayashi Issei Saitoh Masami Watanabe Yasufumi Noguchi
author_facet	Hirofumi Noguchi Koji Sugimoto Chika Miyagi-Shiohira Yoshiki Nakashima Naoya Kobayashi Issei Saitoh Masami Watanabe Yasufumi Noguchi
author_sort	Hirofumi Noguchi
title	RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice
title_short	RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice
title_full	RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice
title_fullStr	RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice
title_full_unstemmed	RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice
title_sort	rcan-11r peptide provides immunosuppression for fully mismatched islet allografts in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d0a1298d24d44d60b856dbc18ce5f181
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RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice

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