Amelioration of Experimental autoimmune encephalomyelitis and DSS induced colitis by NTG-A-009 through the inhibition of Th1 and Th17 cells differentiation

Scientific Reports
Suman AcharyaJae-Hoon Chang

Abstract

CD4+ T cells are the central for the mammalian adaptive immune system. Naïve CD4+ T cells mainly differentiate in to pro-inflammatory Th1, Th2 and Th17 cells upon antigenic stimulation. IFN-γ secreting Th1 cells and IL-17 secreting Th17 cells are found to play key roles in autoimmune diseases like multiple sclerosis (MS) and ulcerative colitis (UC). In this study we found NTG-A-009, 6-aminopyridin-3-ol, has great inhibitory effect on in vitro differentiation of Th1 and Th17 cells without affecting regulatory T cells. Moreover, NTG-A-009 had no effect on CD4+ T cell proliferation and viability. In vivo treatment has shown that NTG-A-009 has ameliorated experimental autoimmune encephalomyelitis (EAE) and dextran sulfate sodium (DSS) induced colitis through the inhibition of Th1 and Th17 cells differentiation. Mechanistically, NTG-A-009 suppressed Th1 and Th17 cells differentiation via the modulation of JAK/STAT signaling pathway. Thus, our data demonstrated that NTG-A-009 ameliorated inflammation through the inhibition of Th1 and Th17 cells generation making it a potential therapeutic candidate for the treatment of inflammatory diseases.

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Citations

Apr 26, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Suman AcharyaJae-Hoon Chang
Aug 22, 2020·World Journal of Gastroenterology : WJG·Friederike CordesDominik Bettenworth
Aug 4, 2020·Bioorganic Chemistry·Chhabi Lal ChaudharyByeong-Seon Jeong
Jan 1, 2021·Journal of Immunology Research·Jun-Bin YanBei-Hui He
Aug 4, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Bhuwan Prasad AwasthiByeong-Seon Jeong

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Methods Mentioned

BETA
flow cytometry
FACS
transgenic
biopsies
transfection
protein assay
PCR

Software Mentioned

Graph Pad Prism
ImageJ
FlowJo

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