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 language | English |
|---|---|
| Pages (from-to) | 32-41 |
| Number of pages | 10 |
| Journal | Molecular Therapy - Methods and Clinical Development |
| Volume | 16 |
| DOIs | |
| State | Published - 2020 Mar 13 |
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Keywords
- Cell penetrating peptide (CPP)
- Multiple sclerosis (MS)
- T cell
- VIVIT
- dNP2
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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 journal › Article
TY - JOUR
T1 - NFAT-Specific Inhibition by dNP2-VIVITAmeliorates Autoimmune Encephalomyelitisby Regulation of Th1 and Th17
AU - Lee, Hong Gyun
AU - Kim, Li Kyung
AU - Choi, Je Min
PY - 2020/3/13
Y1 - 2020/3/13
N2 - 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.
AB - 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.
KW - Cell penetrating peptide (CPP)
KW - Multiple sclerosis (MS)
KW - T cell
KW - VIVIT
KW - dNP2
UR - http://www.scopus.com/inward/record.url?scp=85074464258&partnerID=8YFLogxK
U2 - 10.1016/j.omtm.2019.10.006
DO - 10.1016/j.omtm.2019.10.006
M3 - Article
AN - SCOPUS:85074464258
VL - 16
SP - 32
EP - 41
JO - Molecular Therapy - Methods and Clinical Development
JF - Molecular Therapy - Methods and Clinical Development
SN - 2329-0501
ER -