AUTHOR=Hao Xiaohua , Li Yufeng , Wang Jianwen , Ma Jiali , Zhao Shuli , Ye Xiaohui , He Lingling , Yang Junru , Gao Meixin , Xiao Fan , Wei Hongshan TITLE=Deficient O-GlcNAc Glycosylation Impairs Regulatory T Cell Differentiation and Notch Signaling in Autoimmune Hepatitis JOURNAL=Frontiers in Immunology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02089 DOI=10.3389/fimmu.2018.02089 ISSN=1664-3224 ABSTRACT=Post-translational modifications such as glycosylation play an important role in the function of homeostatic proteins, and are critical driving factors of several diseases; however, the role of glycosylation in autoimmune hepatitis is poorly understood. Here, we established an O-GlcNAc glycosylation-deficient rat model by knocking out the Eogt gene with TALEN-mediated gene targeting. The O-GlcNAc glycosylation deficiency clearly aggravated the liver injury in concanavalin-A induced autoimmune hepatitis, and delayed self-recovery of the liver. Moreover, flow cytometry analysis demonstrated increased infiltration of CD4+ T cells in the livers of rats with O-GlcNAc glycosylation deficiency, and the normal differentiation of T regulatory cells (Tregs) in the liver to inhibit T cell infiltration could not be activated. Furthermore, in vitro experiments showed that O-GlcNAc glycosylation deficiency impaired the differentiation of Tregs to inhibit activation of the Notch signaling pathway in CD4+ T cells. This finding implies that O-GlcNAc glycosylation plays a critical role in activation of Notch signaling, which could promote the differentiation of Tregs in the liver to inhibit T cells infiltration and control disease development in autoimmune hepatitis. Therefore, this study reveals a regulatory role of glycosylation in the pathogenesis of autoimmune hepatitis, and highlights glycosylation as a potential treatment target.