title: Ligation of metabotropic glutamate receptor 3 (Grm3) ameliorates lupus-like disease by reducing B cells.
abstract: Recently B-cell activating factor (BAFF) was identified by our group and others as a novel therapeutic target for the treatment of autoimmune diseases. To expand upon this, we utilized microarrays to screen for molecules upregulated in B cells from BAFF-inhibited mice with lupus-like disease and identified metabotropic glutamate receptor 3 (Grm3). In addition to confirming the expression of this receptor in B cells, a synthetic agonist of Grm3 was found to downregulate B cells and ameliorate autoimmune symptoms in mice. Conversely, a Grm3 antagonist increased B-cell numbers and further aggravated disease. Thus, these results suggest that activation of Grm3 ameliorates lupus-like disease in mice by reducing B cell numbers. Not only do the findings presented in this study increase our understanding of the inhibitory signals initiated on the surface of B cells, but they also identify a novel potential target for the treatment of autoimmune diseases.
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; Department of Rheumatology, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; Department of Mephrology, The 307th Hospital of Chinese People's Liberation Army, Beijing 100850, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xing
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310013, China.
authors.forename: Yinxiang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: yinher2001@yahoo.com.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: wang_renxi@yahoo.com.
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3
keywords: B cells; BAFF; Grm3; Lupus; TACI