PMID- 24644005 OWN - NLM STAT- MEDLINE DCOM- 20140909 LR - 20160511 IS - 2326-5205 (Electronic) IS - 2326-5191 (Linking) VI - 66 IP - 7 DP - 2014 Jul TI - Intravenous immunoglobulin attenuates experimental autoimmune arthritis by inducing reciprocal regulation of Th17 and Treg cells in an interleukin-10-dependent manner. PG - 1768-78 LID - 10.1002/art.38627 [doi] AB - 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 Fcgamma receptor IIB expression. The treatment effects of IVIG on arthritis were lost in IL-10-knockout mice. CONCLUSION: These results showed that IVIG has therapeutic effects by modulating CD4+ T cell differentiation. The therapeutic effects of IVIG are dependent on IL-10. CI - Copyright (c) 2014 by the American College of Rheumatology. FAU - Lee, Seon-Yeong AU - Lee SY AD - Catholic University of Korea, Seoul, South Korea. FAU - Jung, Young-Ok AU - Jung YO FAU - Ryu, Jun-Geol AU - Ryu JG FAU - Kang, Chang-Min AU - Kang CM FAU - Kim, Eun-Kyung AU - Kim EK FAU - Son, Hye-Jin AU - Son HJ FAU - Yang, Eun-Ji AU - Yang EJ FAU - Ju, Ji-Hyeon AU - Ju JH FAU - Kang, Young-Sun AU - Kang YS FAU - Park, Sung-Hwan AU - Park SH FAU - Kim, Ho-Youn AU - Kim HY FAU - Cho, Mi-La AU - Cho ML LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Fcgr2b protein, mouse) RN - 0 (IL10 protein, mouse) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Receptors, IgG) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Arthritis, Experimental/*drug therapy/immunology MH - Autoimmune Diseases/*drug therapy/immunology MH - B-Lymphocytes/cytology/immunology MH - Flow Cytometry MH - Immunoglobulins, Intravenous/*pharmacology MH - Interleukin-10/*immunology MH - Male MH - Mice MH - Mice, Inbred DBA MH - Receptors, IgG/genetics/immunology MH - Severity of Illness Index MH - T-Lymphocytes, Regulatory/cytology/*drug effects/immunology MH - Th17 Cells/cytology/*drug effects/immunology MH - Up-Regulation/drug effects/immunology EDAT- 2014/03/20 06:00 MHDA- 2014/09/10 06:00 CRDT- 2014/03/20 06:00 PHST- 2013/05/30 00:00 [received] PHST- 2014/03/11 00:00 [accepted] PHST- 2014/03/20 06:00 [entrez] PHST- 2014/03/20 06:00 [pubmed] PHST- 2014/09/10 06:00 [medline] AID - 10.1002/art.38627 [doi] PST - ppublish SO - Arthritis Rheumatol. 2014 Jul;66(7):1768-78. doi: 10.1002/art.38627.