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

• Published in: Scientific reports 2018-05, Vol.8 (1), p.7799-14, Article 7799
• Main Authors: Acharya, Suman, Timilshina, Maheshwor, Jiang, Liyuan, Neupane, Sabita, Choi, Dong-Young, Park, Sang Won, Lee, Sang Yeul, Jeong, Byeong-Seon, Kim, Jung-Ae, Nam, Tae-gyu, Chang, Jae-Hoon
• Format: Article
• Language: English
• Subjects: 13/1; 13/2; 13/21; 13/31; 38/90; 631/250/1619/554/1898; 631/250/38; Aminopyridines - pharmacology; Animals; Autoimmune diseases; CD4 antigen; Cell Differentiation - drug effects; Cell proliferation; Colitis - drug therapy; Colitis - prevention & control; Colon; Dextran; Dextran sulfate; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Experimental allergic encephalomyelitis; Helper cells; Humanities and Social Sciences; Immune system; Immunoregulation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory diseases; Interleukin 17; Lymphocytes; Lymphocytes T; Mice; multidisciplinary; Multiple sclerosis; Science; Science (multidisciplinary); Signal Transduction; Sodium; Sulfates; T cell receptors; Th1 Cells - cytology; Th1 Cells - drug effects; Th17 Cells - cytology; Th17 Cells - drug effects; Ulcerative colitis; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-26088-y

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.