title: IK acts as an immunoregulator of inflammatory arthritis by suppressing TH17 cell differentiation and macrophage activation.
abstract: Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, 420-743, Korea.
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Park
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan, 570-752, Korea.
authors.forename: Sang-Myeong
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul,137-040, Korea.
authors.forename: Jun-Ki
authors.initials: JK
authors.lastname: Min
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul,137-040, Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Moon
authors.affiliation: Department of Medicine, College of Medicine, University of Ulsan, Seoul 138-736, Korea.
authors.forename: Inki
authors.initials: I
authors.lastname: Kim
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan, 570-752, Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Kang
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, 420-743, Korea.
authors.forename: Sooho
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, 420-743, Korea.
authors.forename: SeulGi
authors.initials: S
authors.lastname: Choi
authors.affiliation: Biomaterials Research Center, Cellinbio, Suwon, 443-734, Korea.
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Jung
authors.affiliation: Biomaterials Research Center, Cellinbio, Suwon, 443-734, Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, 420-743, Korea.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Nam
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; C484250:Ik protein, mouse