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). Previously, we have shown that some 6-aminotrimethylpyridin-3-ol analogues have anti-colitis activity both in vitro and in vivo models. In this study we found 1,3,4-thiadiazole tethering 6-aminopyridin-3-ol derivatives have great inhibitory effect on in vitro differentiation of Th1 and Th17 cells without affecting regulatory T cells. Moreover, the derivatives had no effect on CD4+ T cell proliferation and viability. In vivo treatment has shown that the derivatives has ameliorated experimental autoimmune encephalomyelitis (EAE) and dextran sulfate sodium (DSS) induced colitis through the inhibition of Th1 and Th17 cells differentiation. Mechanistically, the derivatives suppressed Th1 and Th17 cells differentiation via the modulation of JAK/STAT signaling pathway. Thus, our data demonstrated that the derivatives ameliorated inflammation through the inhibition of Th1 and Th17 cells generation making it a potential therapeutic candidate for the treatment of inflammatory diseases.

Amelioration of experimental autoimmune encephalomyelitis and DSS-induced colitis by thiadiazole derivatives of 6-aminopyridin-3ol through the inhibition of Th1 and Th17 cells differentiation

2019 Fall National Meeting

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