Hsp90通过调节Jagged-1/Notch信号通路抑制Th22细胞分化（英文）

【作者】 史圣楠； 曾博宁； 邹海玲； 熊永佳； 李筠； 蔡镇隆； 席名昕； 王丹； 康亚玲； 刘宁； 罗琪； 曾山； 肖浦； 刘静； 邢飞跃；

【机构】 暨南大学免疫生物学系组织移植与免疫研究中心； 暨南大学口腔医学院口腔修复学系； 暨南大学肿瘤分子生物学教育部重点实验室；

【摘要】 Our previous results proved that Jagged-1/Notch signaling inhibits the phenotypic transformation of naive CD4+T cells into Th22 induced by both IL-6 and TNF-α.The current study showed that this process was facilitated by hsp90 knockdown or SNX2112 with the augment of il-22,ahr and arnt,the attenuation of hes-1 as well as the high productions of Th22 cytokines and CCR6,which could be reversed by Hsp90 overexpression or GGA.Although Jagged-1 or DAPT caused downregulation or upregulation of Th22 phenotype,no changes were observed at the levels of Hsp90 mRNA and protein.Furthermore,the inhibition or activation of Hsp90 was able to reduce or enhance downstream Hes-1 via interacting with NICD and AhR.The in vivo overexpression of Hsp90 could suppress deviation of Th22,which were rescued by hsp90 knockdown.These data demonstrate that Hsp90 can stabilize NICD and AhR to boost Notch signaling transduction,suggesting that it regulates Notch signaling to mediate Th22 differentiation.更多还原

【Abstract】 Our previous results proved that Jagged-1/Notch signaling inhibits the phenotypic transformation of naive CD4+T cells into Th22 induced by both IL-6 and TNF-α.The current study showed that this process was facilitated by hsp90 knockdown or SNX2112 with the augment of il-22,ahr and arnt,the attenuation of hes-1 as well as the high productions of Th22 cytokines and CCR6,which could be reversed by Hsp90 overexpression or GGA.Although Jagged-1 or DAPT caused downregulation or upregulation of Th22 phenotype,no changes were observed at the levels of Hsp90 mRNA and protein.Furthermore,the inhibition or activation of Hsp90 was able to reduce or enhance downstream Hes-1 via interacting with NICD and AhR.The in vivo overexpression of Hsp90 could suppress deviation of Th22,which were rescued by hsp90 knockdown.These data demonstrate that Hsp90 can stabilize NICD and AhR to boost Notch signaling transduction,suggesting that it regulates Notch signaling to mediate Th22 differentiation.更多还原