Cell permeable NFAT inhibitory peptide Sim-2-VIVIT inhibits T-cell activation and alleviates allergic airway inflammation and hyper-responsiveness

Immunology Letters
Je-Min ChoiSang-Kyou Lee

Abstract

Nuclear factor of activated T cells (NFAT) is an important transcription factor for the production of interleukin (IL)-2 upon T-cell receptor (TcR) signaling. Therefore, inhibition of the NFAT-carcineurin pathway is an important target for inflammatory disease inhibition and graft rejection. A novel cell permeable peptide (CPP), Sim-2, has been identified from a human transcription factor, and Sim-2-CPP conjugated to β-galactosidase or EGFP protein was efficiently delivered into cells in vitro and in vivo. A cell permeable form of the NFAT inhibitory peptide VIVIT (Sim-2-VIVIT) was synthesized and showed inhibitory effects on human CD4 or CD8 T-cell activation through NFAT transcriptional activity suppression and IL-2 inhibition. Intranasal administration of the Sim-2-VIVIT peptide in an ovalbumin (OVA)-induced murine asthma model alleviated peribronchial and perivascular infiltration of inflammatory cells in the lung and caused airway remodeling and airway hyper-responsiveness. These results suggest that cell permeable Sim-2-VIVIT peptide has clinical potential as an immunosuppressive agent for inflammatory diseases.

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Citations

May 13, 2014·Journal of Pharmacological and Toxicological Methods·Enrico DavoliTiziana Borsello
May 20, 2015·Blood·Christian A FernandezMary V Relling
Jan 24, 2017·Future Medicinal Chemistry·Aleksandra Ellert-MiklaszewskaBozena Kaminska
Mar 5, 2016·Immune Network·Sangho LimJe-Min Choi
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Noriko KitamuraOsamu Kaminuma
Jan 19, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mengyang XuDaoguang Yan
Mar 6, 2017·Drug Metabolism and Personalized Therapy·Maria Lopez-SantillanAfrica Garcia-Orad
Dec 13, 2018·Frontiers in Immunology·Jae-Ung LeeJe-Min Choi
Jun 28, 2018·Frontiers in Immunology·Johannes BaurAndris Avots
Nov 19, 2019·Molecular Therapy. Methods & Clinical Development·Hong-Gyun LeeJe-Min Choi
Apr 4, 2021·International Journal of Molecular Sciences·Noriko Kitamura, Osamu Kaminuma
Apr 7, 2021·The Journal of Clinical Investigation·Shizuka OtsukaJonathan D Ashwell
Oct 20, 2020·Journal of Medicinal Chemistry·Patrick G DoughertyDehua Pei
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aleksandra Ellert-MiklaszewskaBozena Kaminska

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