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NFAT specific inhibition in T cells ameliorates experimental autoimmune encephalomyelitis by regulation of Th1 and Th17 cell differentiation

Title
NFAT specific inhibition in T cells ameliorates experimental autoimmune encephalomyelitis by regulation of Th1 and Th17 cell differentiation
Other Titles
NFAT 특이적 억제를 통한 Th1 및 Th17 분화조절에 따른 다발성경화증 치료에 대한 연구
Author
Li-Kyung Kim
Alternative Author(s)
김리경
Advisor(s)
최제민
Issue Date
2019-02
Publisher
한양대학교
Degree
Master
Abstract
Nuclear factor of activated T cells (NFAT) is an important transcription factor for T-cell activation and proliferation. Recently, NFAT has been more highlighted to control specific gene expressions in differentiation of CD4 T helper subsets including T helper 1 (Th1), Th2, Th17, regulatory T (Treg), and follicular helper T cells (Tfh). Therefore, regulation of NFAT role could be an important strategy to change T cell fate and applying for autoimmune diseases. To modulate NFAT function in T cells, we utilized NFAT inhibitory peptide, VIVIT conjugated with a cell penetrating peptide dNP2, which could across through blood-brain barrier. NFAT inhibition by dNP2-VIVIT peptide treatment in mouse naïve CD4 T cells showed significant inhibitory effects on T cell differentiation into Th1 and Th17 cells without affecting regulatory T cells, whereas Cyclosporine A inhibits regulatory T cell differentiation as well as Th1 and Th17 cells. Next, we proved that dNP2- VIVIT treatment to experimental autoimmune encephalomyelitis (EAE) mice reduced disease severity and demyelination with decreased CNS-infiltrating IFN-γ and IL-17 producing CD4+ T cells with comparable amount of Foxp3 expressing cells. Moreover, dNP2-VIVIT treatment to NP-OVA immunized mice showed decreased CXCR5+Bcl6+ Tfh cells. Collectively, these results suggest that NFAT specific inhibition by VIVIT peptide delivery in T cells could be a T cell modulatory drug for autoimmune diseases like multiple sclerosis.
URI
http://dcollection.hanyang.ac.kr/common/orgView/000000108961http://repository.hanyang.ac.kr/handle/20.500.11754/99332
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > LIFE SCIENCE(생명과학과) > Theses (Master)
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