Interleukin-2/anti-interleukin-2 monoclonal antibody immune complex suppresses collagen-induced arthritis in mice by fortifying interleukin-2/STAT5 signalling pathways

被引：54

作者：

Lee, Seon-Yeong ^{[1
]}

Cho, Mi-La ^{[1
]}

Oh, Hye-Jwa ^{[1
]}

Ryu, Jun-Geol ^{[1
]}

Park, Min-Jung ^{[1
]}

Jhun, Joo-Yeon ^{[1
]}

Park, Mi-Kyung ^{[1
]}

Stone, John C. ^{[2
]}

Ju, Ji-Hyun ^{[1
,3
]}

Hwang, Sue-Yun ^{[4
]}

Park, Sung-Hwan ^{[1
,3
]}

Surh, Charles D. ^{[2
,5
]}

Kim, Ho-Youn ^{[1
,3
]}

机构：

[1] Catholic Univ Korea, Rheumatism Res Ctr, Catholic Inst Med Sci, Seoul 137040, South Korea

[2] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[3] Catholic Univ Korea, Ctr Rheumat Dis, Div Rheumatol, Dept Internal Med,Seoul St Marys Hosp, Seoul 137040, South Korea

[4] Hankyong Natl Univ, Grad Sch Bio&Informat Technol, Inst Genet Engn, Ansung, South Korea

[5] POSTECH WCU, Div IBB, Pohang, South Korea

来源：

IMMUNOLOGY | 2012年 / 137卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

interleukin-2 immune complex; regulatory T cell; rheumatoid arthritis; signal transducer and activator of transcription 5; T helper type 17; REGULATORY T-CELLS; IMMUNOLOGICAL SELF-TOLERANCE; GERMINAL CENTER REACTIONS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; ORAL TOLERANCE; II COLLAGEN; INDUCTION; IL-17; STAT5;

D O I：

10.1111/imm.12008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：305 / 316

页数：12

共 45 条

[1] T regulatory cells participate in the control of germinal centre reactions [J].