title: A truncated IL-12rβ1 receptor ameliorates chronic graft-versus-host disease-induced lupus nephritis by inhibiting Th1 and Th17 cells.
abstract: Th1 and Th17 cells have been strongly implicated in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-12 and IL-23 respectively drive the polarization of Th1 and Th17 cells and share a common p40 subunit. In this study, the protective and therapeutic effects of a truncated human IL-12rβ1 receptor (tIL12rβ1) targeting IL-12/IL-23 p40 were evaluated in chronic graft-versus-host disease (cGVHD)-induced SLE-like model. The results indicated that tIL12rβ1 treatment effectively delayed the proteinuria onset and induced a significant remission of proteinuria, autoantibody production, and immune complex deposition in the mouse model. Remarkably, the therapeutic effects of tIL12rβ1 were predominantly dependent on the suppression of pathogenic Th1 and Th17 cell commitment through the reduction of RORγt and T-bet expression. Collectively, this receptor molecule may offer a new treatment option for SLE.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xdgao@cpu.edu.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: wbyao@cpu.edu.cn.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Yao
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011507:Proteinuria / Q000188:drug therapy; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects*
chemical_list: D016207:Cytokines; C508438:IL12RB1 protein, human; D053707:Receptors, Interleukin-12
keywords: Chronic graft-versus host disease; IL-17; IL-23R; Lupus nephritis