Immunoproteasome activation in immune cells is involved in the modulation of immune responses.Increasing evidence indicates that proteasome inhibitors show beneficial effects in treating autoimmune diseases,but it rem...Immunoproteasome activation in immune cells is involved in the modulation of immune responses.Increasing evidence indicates that proteasome inhibitors show beneficial effects in treating autoimmune diseases,but it remains unclear whether proteasome inhibition is an effective approach for suppressing autoimmune development in Sjögren’s syndrome(SS).Our previous work has demonstrated a critical role for Th17 cells in the development of experimental SS(ESS)in mice.In this study,we detected high levels of low-molecular-weight protein 7(LMP7),a key subunit of the immunoproteasome,in Th17 cells from ESS mice.Moreover,treatment with bortezomib(BTZ),a proteasome inhibitor,markedly suppressed Th17 differentiation in both murine and human naive T cells in culture.Furthermore,ESS mice treated with BTZ displayed significantly higher saliva flow rates and a reduction in tissue destruction in the salivary glands compared with vehicle-treated ESS mice.Notably,BTZ-treated ESS mice showed markedly decreased Th17 cells,germinal center B cells and plasma cells in the peripheral lymphoid organs.In addition,adoptively transferred wild type naive CD4+T cells rapidly differentiated into Th17 cells and induced salivary dysfunction in IL-17-deficient mice immunized for ESS induction.However,BTZ treatment profoundly suppressed the donor T-cell-derived Th17 response and ameliorated the reduction in salivary secretion in IL-17-deficient recipient mice.Taken together,our findings demonstrate that proteasome inhibition can effectively ameliorate ESS by suppressing the Th17 response,which may contribute to the development of a novel therapeutic strategy for the treatment of SS.展开更多
Theauthor treated 148 cases of hiccup by finger-pressing Yifeng (TE 17). After one treatment, 97cases were cured; 34 cases were cured after 2-3 treatments, 6 cases were cured after over 4 treatments; and 11 cases obta...Theauthor treated 148 cases of hiccup by finger-pressing Yifeng (TE 17). After one treatment, 97cases were cured; 34 cases were cured after 2-3 treatments, 6 cases were cured after over 4 treatments; and 11 cases obtained no effect. The total effective rate was 92.6%.展开更多
基金by grants from the National Natural Science Foundation of China(81373195,91442116,81601424 and 31300739)the National Basic Research Program(No.2014CB541904)+3 种基金the Natural Science Foundation of Jiangsu(Grant No.BK20150533)the General Research Fund,Hong Kong Research Grants Council(No.1711451517149716)and the Hong Kong Croucher Foundation(260960116).
文摘Immunoproteasome activation in immune cells is involved in the modulation of immune responses.Increasing evidence indicates that proteasome inhibitors show beneficial effects in treating autoimmune diseases,but it remains unclear whether proteasome inhibition is an effective approach for suppressing autoimmune development in Sjögren’s syndrome(SS).Our previous work has demonstrated a critical role for Th17 cells in the development of experimental SS(ESS)in mice.In this study,we detected high levels of low-molecular-weight protein 7(LMP7),a key subunit of the immunoproteasome,in Th17 cells from ESS mice.Moreover,treatment with bortezomib(BTZ),a proteasome inhibitor,markedly suppressed Th17 differentiation in both murine and human naive T cells in culture.Furthermore,ESS mice treated with BTZ displayed significantly higher saliva flow rates and a reduction in tissue destruction in the salivary glands compared with vehicle-treated ESS mice.Notably,BTZ-treated ESS mice showed markedly decreased Th17 cells,germinal center B cells and plasma cells in the peripheral lymphoid organs.In addition,adoptively transferred wild type naive CD4+T cells rapidly differentiated into Th17 cells and induced salivary dysfunction in IL-17-deficient mice immunized for ESS induction.However,BTZ treatment profoundly suppressed the donor T-cell-derived Th17 response and ameliorated the reduction in salivary secretion in IL-17-deficient recipient mice.Taken together,our findings demonstrate that proteasome inhibition can effectively ameliorate ESS by suppressing the Th17 response,which may contribute to the development of a novel therapeutic strategy for the treatment of SS.
文摘Theauthor treated 148 cases of hiccup by finger-pressing Yifeng (TE 17). After one treatment, 97cases were cured; 34 cases were cured after 2-3 treatments, 6 cases were cured after over 4 treatments; and 11 cases obtained no effect. The total effective rate was 92.6%.
