최제민
Li-Kyung Kim
2019-02-28T03:01:08Z
2019-02-28T03:01:08Z
2019-02
https://repository.hanyang.ac.kr/handle/20.500.11754/99332
http://hanyang.dcollection.net/common/orgView/200000434634
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.
한양대학교
NFAT specific inhibition in T cells ameliorates experimental autoimmune encephalomyelitis by regulation of Th1 and Th17 cell differentiation
NFAT 특이적 억제를 통한 Th1 및 Th17 분화조절에 따른 다발성경화증 치료에 대한 연구
Theses
김리경
김리경
S
대학원
생명과학과
Master