title: Interleukin-2/anti-interleukin-2 monoclonal antibody immune complex suppresses collagen-induced arthritis in mice by fortifying interleukin-2/STAT5 signalling pathways.
abstract: In this study, we investigated the effects of administration of interleukin-2 (IL-2)/JES6-1 (anti-IL-2 monoclonal antibody) immune complexes on the expansion and activation of regulatory T (Treg) cells, the down-regulation of T helper type 17 (Th17) cells, and the control of the severity of collagen-induced arthritis (CIA). Wild-type and CIA-induced wild-type mice were injected intraperitoneally (i.p.) with IL-2 or IL-2/JES6-1 complex three times at 2-day intervals. Treg cell surface markers were analysed by flow cytometry. After injecting IL-2 or IL-2/JES6-1, the time kinetics of IL-2 signalling molecules was examined by FACS and Western blotting. Concentrations of IL-17 and IL-10 were measured by ELISA. Injection of IL-2/JES6-1 increased the proportion of Foxp3+ Treg cells among splenic CD4+ T cells, which reached the highest level on day 4 after injection. Up-regulation of CTLA4, GITR and glycoprotein-A repetitions predominant (GARP) was observed. Activation of p-signal transducer and activator of transcription 5 (STAT5) was apparent within 3 hr after injection of IL-2/JES6-1 complexes. Expression of IL-2 signalling molecules, including p-AKT and p-p38/mitogen-activated protein kinase, was also higher in splenocytes treated with IL-2/JES6-1 complexes. Injection of IL-2/JES6-1 complexes suppressed the induction of CIA and the production of IL-17 and inflammatory responses while increasing the level of IL-10 in the spleen. The expansion of Treg cells (via STAT5) and the concomitant increase in IL-2 signalling pathways by IL-2/JES6-1 complexes suggests their potential use as a novel therapeutic agent for the treatment of autoimmune arthritis.
authors.affiliation: The Rheumatism Research Centre, Catholic Research Institute of Medical Science, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, South Korea.
authors.forename: Seon-Yeong
authors.initials: SY
authors.lastname: Lee
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Hye-Jwa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Jun-Geol
authors.initials: JG
authors.lastname: Ryu
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Jhun
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: John C
authors.initials: JC
authors.lastname: Stone
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Ju
authors.forename: Sue-Yun
authors.initials: SY
authors.lastname: Hwang
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D007376:Interleukin-2 / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D050799:STAT5 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D058504:Th17 Cells / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007376:Interleukin-2; D050799:STAT5 Transcription Factor