title: A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice.
abstract: Interleukin-12 family cytokines have emerged as critical regulators of immunity with some members (IL-12, IL-23) associated with disease pathogenesis while others (IL-27, IL-35) mitigate autoimmune diseases. Each IL-12 family member is comprised of an α and a β chain, and chain-sharing is a key feature. Although four bona fide members have thus far been described, promiscuous chain-pairing between alpha (IL-23p19, IL-27p28, IL-12/IL-35p35) and beta (IL-12/IL-23p40, IL-27/IL-35Ebi3) subunits, predicts six possible heterodimeric IL-12 family cytokines. Here, we describe a new IL-12 member composed of IL-23p19 and Ebi3 heterodimer (IL-39) that is secreted by LPS-stimulated B cells and GL7(+) activated B cells of lupus-like mice. We further show that IL-39 mediates inflammatory responses through activation of STAT1/STAT3 in lupus-like mice. Taken together, our results show that IL-39 might contribute to immunopathogenic mechanisms of systemic lupus erythematosus, and could be used as a possible target for its treatment.
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.|Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yinxiang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.|Department of Nephrology, The 307th Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.|College of Pharmacy, Henan University, Kaifeng, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Rheumatology, First hospital of Jilin University, Changchun, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Egwuagu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D016130:Immunophenotyping; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D053760:Interleukin-23 Subunit p19 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D015778:Minor Histocompatibility Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C499601:Ebi3 protein, mouse; D053760:Interleukin-23 Subunit p19; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C528688:interleukin-23 receptor, mouse
keywords: Autoimmunity ⋅ IL-12 ⋅ IL-23p19 ⋅ IL-27/IL-35Ebi3 ⋅ IL-39 ⋅ Inflammation ⋅ Systemic lupus erythematosus