title: Nuclear Factor Erythroid 2-related Factor 2 Deficiency Exacerbates Lupus Nephritis in B6/lpr mice by Regulating Th17 Cell Function.
abstract: Lupus nephritis (LN) is the major clinical manifestation of systemic lupus erythematosus. LN is promoted by T helper 17 (Th17) cells, which are the major pro-inflammatory T cell subset contributing to autoimmunity regulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is critical for suppressing reactive oxygen species (ROS) and relieving oxidant stress by regulating antioxidant gene expression. Previous studies have demonstrated that Nrf2 deficiency promotes drug-induced or spontaneous LN. However, whether NRF2 regulates Th17 function during LN development is still unclear. In this study, we introduced Nrf2 deficiency into a well-known LN model, the B6/lpr mouse strain, and found that it promoted early-stage LN with altered Th17 activation. Th17 cells and their relevant cytokines were dramatically increased in these double-mutant mice. We also demonstrated that naïve T cells from the double-mutant mice showed significantly increased differentiation into Th17 cells in vitro, with decreased expression of the Th17 differentiation suppressor Socs3 and increased phosphorylation of STAT3. Our results demonstrated that Nrf2 deficiency promoted Th17 differentiation and function during LN development. Moreover, our results suggested that the regulation of Th17 differentiation via NRF2 could be a therapeutic target for the treatment of subclinical LN patients.
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Ministry of Education in China, Guangzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Ministry of Education in China, Guangzhou, China.
authors.forename: Huanpeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Ministry of Education in China, Guangzhou, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Ministry of Education in China, Guangzhou, China.
authors.forename: Xiaoxie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Bolan
authors.initials: B
authors.lastname: Yu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Ministry of Education in China, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D016131:Lymphocyte Subsets / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency* / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis; D058504:Th17 Cells
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016207:Cytokines; D051267:NF-E2-Related Factor 2