NFAT-Specific Inhibition by dNP2-VIVITAmeliorates Autoimmune Encephalomyelitisby Regulation of Th1 and Th17

Hong Gyun Lee, Li Kyung Kim, Je Min Choi

Research output: Contribution to journalArticle

Abstract

Nuclear factor of activated T cells (NFATs) is an important transcription factor for T cell activation and proliferation. Recent studies have highlighted the role of NFATs in regulating the differentiation of effector CD4 T helper (Th) subsets including Th1 and Th17 cells. Because controlling the effector T cell function is important for the treatment of autoimmune diseases, regulation of NFAT functions in T cells would be an important strategy to control the pathogenesis of autoimmune diseases. Here, we demonstrated that an NFAT inhibitory peptide, VIVIT conjugated to dNP2 (dNP2-VIVIT), a blood-brain barrier-permeable peptide, ameliorated experimental autoimmune encephalomyelitis (EAE) by inhibiting Th1 and Th17 cells, but not regulatory T (Treg) cells. dNP2-VIVIT negatively regulated spinal cord-infiltrating interleukin-17A (IL-17A) and interferon (IFN)-γ-producing CD4+ T cells without affecting the number of Foxp3+ CD4+ Treg cells, whereas dNP2-VEET or 11R-VIVIT could not significantly inhibit EAE. In comparison with cyclosporin A (CsA), dNP2-VIVIT selectively inhibited Th1 and Th17 differentiation, whereas CsA inhibited the differentiation of all T cell subsets including that of Th2 and Treg cells. Collectively, this study demonstrated the role of dNP2-VIVIT as a novel agent for the treatment of autoimmune diseases such as multiple sclerosis by regulating the functions of Th1 and Th17 cells.

Original languageEnglish
Pages (from-to)32-41
Number of pages10
JournalMolecular Therapy - Methods and Clinical Development
Volume16
DOIs
StatePublished - 2020 Mar 13

Fingerprint

NFATC Transcription Factors
Regulatory T-Lymphocytes
Th17 Cells
Th1 Cells
Autoimmune Diseases
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Cyclosporine
Th2 Cells
Interleukin-17
T-Lymphocyte Subsets
Blood-Brain Barrier
Interferons
Multiple Sclerosis
Spinal Cord
Transcription Factors
Cell Proliferation
Peptides

Keywords

  • Cell penetrating peptide (CPP)
  • Multiple sclerosis (MS)
  • T cell
  • VIVIT
  • dNP2

Cite this

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NFAT-Specific Inhibition by dNP2-VIVITAmeliorates Autoimmune Encephalomyelitisby Regulation of Th1 and Th17. / Lee, Hong Gyun; Kim, Li Kyung; Choi, Je Min.

In: Molecular Therapy - Methods and Clinical Development, Vol. 16, 13.03.2020, p. 32-41.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Lee, Hong Gyun

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