Interleukin-2/anti-interleukin-2 monoclonal antibody immune complex suppresses collagen-induced arthritis in mice by fortifying interleukin-2/STAT5 signalling pathways
SCIE
SCOPUS
- Title
- Interleukin-2/anti-interleukin-2 monoclonal antibody immune complex suppresses collagen-induced arthritis in mice by fortifying interleukin-2/STAT5 signalling pathways
- Authors
- Lee, SY; Cho, ML; Oh, HJ; Ryu, JG; Park, MJ; Jhun, JY; Park, MK; Stone, JC; Ju, JH; Hwang, SY; Park, SH; Surh, CD; Kim, HY
- Date Issued
- 2012-12
- Publisher
- Wiley-Blackwell Publishing Ltd.
- 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.
- Keywords
- 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
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/15176
- DOI
- 10.1111/IMM.12008.
- ISSN
- 0019-2805
- Article Type
- Article
- Citation
- Immunology, vol. 137, no. 4, page. 305 - 316, 2012-12
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