title: Intravenous immunoglobulin attenuates experimental autoimmune arthritis by inducing reciprocal regulation of Th17 and Treg cells in an interleukin-10-dependent manner.
abstract: OBJECTIVE
  Intravenous immunoglobulin (IVIG) is used as a therapeutic agent in various autoimmune diseases. The aims of this study were to investigate the therapeutic effects of IVIG on collagen-induced arthritis (CIA) and identify the mechanism responsible for any therapeutic effects.
  
  
  METHODS
  IVIG was administered to mice with CIA, and the in vivo effects were determined. Th17 and Treg cell frequencies were analyzed by flow cytometry, and cytokine levels in the supernatant were measured by enzyme-linked immunosorbent assay. Subpopulations of T cells and B cells in the spleen were assessed by confocal microscopy.
  
  
  RESULTS
  The arthritis severity score and incidence of arthritis were lower in mice treated with IVIG compared with untreated mice. Histopathologic analysis showed less joint damage in mice treated with IVIG. The expression of proinflammatory cytokines, specific type II collagen antibodies, and osteoclast markers was significantly reduced in mice treated with IVIG. Administration of IVIG induced increased FoxP3 expression and inhibited Th17 cell development. The number of FoxP3+ Treg cells was increased, and the number of Th17 cells was decreased in the spleens of mice treated with IVIG. The number of FoxP3+ follicular helper T cells was increased, and subsequent maturation of germinal center B cells was inhibited by IVIG. In addition, IVIG up-regulated interleukin-10 (IL-10) and Fcγ receptor IIB expression. The treatment effects of IVIG on arthritis were lost in IL-10-knockout mice.
  
  
  CONCLUSIONS
  These results showed that IVIG has therapeutic effects by modulating CD4+ T cell differentiation. The therapeutic effects of IVIG are dependent on IL-10.
authors.affiliation: Catholic University of Korea, Seoul, South Korea.
authors.forename: Seon-Yeong
authors.initials: SY
authors.lastname: Lee
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Jung
authors.forename: Jun-Geol
authors.initials: JG
authors.lastname: Ryu
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kang
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Son
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Yang
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Ju
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: C499172:Fcgr2b protein, mouse; C556062:IL10 protein, mouse; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D016753:Interleukin-10