Effect Of Jagged-1 Signaling On The Differentiation Of Th17 Cells

Object:To investigate the effect of Notch signaling on Th17 differentiation through studying the effect of soluble Jagged-1/Fc, an activator of Notch signaling, on peripheral T lymphocyte differentiation in vitro.Method:We treated the lymphocytes with different concentrations of Jagged-1 at the indicated time, then detected the expression of interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10(IL-10), interleukin 17 (IL-17)and interferon-gamma (IFN-γ)in the supernatant of different treatment by the way of ELISA. The influences of Jagged-1 on the expression of NICD,Hes-1 and Deltex-1that contribute to the Jagged-1-Notch downstream signaling and p-STAT3 was checked through western-blot analysis. At last, we evaluated the expression of CD4, IL-17 and IFN-γin mouse peripheral T lymphocyte stimulated by Jagged-1 through double fluorescin-conjugated monoclonal antibody labeling technique together with flow-cytometry.Result:As the Jagged-1 increased, the expression of IL-4 decreased, whereas the expression of IFN-γ,IL-12 increased and reached its peak on the 3rd day. Hes-1 and Deltex-1 expression was up-regulated to the maximum on the 3rd day, on contrary, p-STAT3 decreased with more Jagged-1 stimulation. The expression of 11-17 decreased with more Jagged-1, which can be reversed by DAPT.Conclusion:The result suggests that Jagged-1 can activate Notch signaling pathway and promote the expression of Hes-1 and Deltex-1 as well as IFN-γ,IL-10 but inhibit the expression of p-STAT3,IL-4and IL-17, thus influencing the differentiation of Th17 cells.