Abstract: Objective To investigate the influence of Notch signaling pathway inhibition on interleukin- 22( IL- 22) secreted by CD4~+T cells in patients with hepatitis B,and to elaborate on the role of the Notch- IL- 22 signaling pathway in the pathogenesis of hepatitis B.Methods A total of 45 previously untreated patients with hepatitis B who visited and were hospitalized in Tangdu Hospital from July 2013 to December 2014 were enrolled,and among these patients,13 had acute hepatitis B( AHB) and 32 had chronic hepatitis B( CHB). Another20 healthy volunteers were enrolled as normal control( NC) group. CD4~+T cells were isolated,and quantitative real- time PCR was used to measure the mRNA expression of Notch1 and Notch2. CD4~+T cells were stimulated by anti- CD3 antibody or HBV core peptide library and the Notch signaling pathway inhibitor DAPT was added. Quantitative real- time PCR was used to measure the mRNA expression of IL-22 in cells,and ELISA was used to measure the level of IL- 22 secretory protein in supernatant. The Kruskal- Wallis H test was used for statistical analysis of data between groups,and the Dunn's multiple test was used for data comparison between any two groups. Results The mRNA expression of Notch1 in CD4~+T cells in CHB patients was about 2 times that in NCs( Z = 7. 708,P = 0. 018),and the mRNA expression of Notch2 in AHB and CHB patients was more than 10 times that in NCs( Z = 9. 643 and 12. 90,both P < 0. 000 1). Inhibition of the Notch signaling pathway did not influence the mRNA expression of IL- 22 in cultured CD4~+T cells,but significantly reduced the secretion of non- specific IL- 22 in NCs( Z = 5. 068,P = 0. 015),AHB patients( Z = 5. 203,P = 0. 016),and CHB patients( Z = 2. 892,P = 0. 047). Conclusion Inhibition of the Notch signaling pathway can block IL- 22 secretion by non- specific CD4~+T cells,suggesting that the Notch- IL- 22 signaling pathway may promote non- specific inflammatory response in HBV infection.