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

Hirofumi Noguchi, Koji Sugimoto, Chika Miyagi-Shiohira, Yoshiki Nakashima, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article number3043
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice'. Together they form a unique fingerprint.

  • Cite this

    Noguchi, H., Sugimoto, K., Miyagi-Shiohira, C., Nakashima, Y., Kobayashi, N., Saitoh, I., Watanabe, M., & Noguchi, Y. (2017). RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice. Scientific reports, 7(1), [3043]. https://doi.org/10.1038/s41598-017-02934-3