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


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-? 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.

SUBMITTER: Acharya S 

PROVIDER: S-EPMC5958108 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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

Acharya Suman S   Timilshina Maheshwor M   Jiang Liyuan L   Neupane Sabita S   Choi Dong-Young DY   Park Sang Won SW   Lee Sang Yeul SY   Jeong Byeong-Seon BS   Kim Jung-Ae JA   Nam Tae-Gyu TG   Chang Jae-Hoon JH  

Scientific reports 20180517 1


CD4<sup>+</sup> T cells are the central for the mammalian adaptive immune system. Naïve CD4<sup>+</sup> 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  ...[more]

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