DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice
We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced C...
Saved in:
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2015-01-01
|
Series: | Journal of Immunology Research |
Online Access: | http://dx.doi.org/10.1155/2015/834085 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832552014573207552 |
---|---|
author | Jun-Eui Park Jinah Jang Ji-Hye Choi Mi-sun Kang Yun-Ju Woo Young-Rim Seong Chan-Bum Choi Hye-Soon Lee Sang-Cheol Bae Yong-Soo Bae |
author_facet | Jun-Eui Park Jinah Jang Ji-Hye Choi Mi-sun Kang Yun-Ju Woo Young-Rim Seong Chan-Bum Choi Hye-Soon Lee Sang-Cheol Bae Yong-Soo Bae |
author_sort | Jun-Eui Park |
collection | DOAJ |
description | We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs. The effect of CII-smDCs alone was also comparable to the combination therapy. CD4+Foxp3+ Treg populations and IL-10 secretion markedly increased, and CII-specific autoreactive T cells decreased in mice treated with CII-smDCs alone or in combination with MTX. Combination therapy reduced the secretion of interferon-γ (IFN-γ) and IL-17 with little influence on the IL-4 secretion in the mixed leukocyte reaction. These results imply that the combination therapy with low-dose MTX and smDCs is effective in controlling advanced CIA by enhancing Treg population and suppresses antigen-specific Th1/Th17 immunity, rather than initiating Th1 to Th2 immune deviation. Our findings provide a better understanding of the DC therapy in combination with MTX for the treatment of patients with rheumatoid arthritis (RA). |
format | Article |
id | doaj-art-5f9ac39b011f4ca8b7cfb77e9327079f |
institution | Kabale University |
issn | 2314-8861 2314-7156 |
language | English |
publishDate | 2015-01-01 |
publisher | Wiley |
record_format | Article |
series | Journal of Immunology Research |
spelling | doaj-art-5f9ac39b011f4ca8b7cfb77e9327079f2025-02-03T05:59:46ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/834085834085DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in MiceJun-Eui Park0Jinah Jang1Ji-Hye Choi2Mi-sun Kang3Yun-Ju Woo4Young-Rim Seong5Chan-Bum Choi6Hye-Soon Lee7Sang-Cheol Bae8Yong-Soo Bae9JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of KoreaJW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of KoreaJW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of KoreaJW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of KoreaJW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of KoreaJW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of KoreaDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Republic of KoreaDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Republic of KoreaDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Republic of KoreaJW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of KoreaWe have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs. The effect of CII-smDCs alone was also comparable to the combination therapy. CD4+Foxp3+ Treg populations and IL-10 secretion markedly increased, and CII-specific autoreactive T cells decreased in mice treated with CII-smDCs alone or in combination with MTX. Combination therapy reduced the secretion of interferon-γ (IFN-γ) and IL-17 with little influence on the IL-4 secretion in the mixed leukocyte reaction. These results imply that the combination therapy with low-dose MTX and smDCs is effective in controlling advanced CIA by enhancing Treg population and suppresses antigen-specific Th1/Th17 immunity, rather than initiating Th1 to Th2 immune deviation. Our findings provide a better understanding of the DC therapy in combination with MTX for the treatment of patients with rheumatoid arthritis (RA).http://dx.doi.org/10.1155/2015/834085 |
spellingShingle | Jun-Eui Park Jinah Jang Ji-Hye Choi Mi-sun Kang Yun-Ju Woo Young-Rim Seong Chan-Bum Choi Hye-Soon Lee Sang-Cheol Bae Yong-Soo Bae DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice Journal of Immunology Research |
title | DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice |
title_full | DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice |
title_fullStr | DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice |
title_full_unstemmed | DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice |
title_short | DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice |
title_sort | dc based immunotherapy combined with low dose methotrexate effective in the treatment of advanced cia in mice |
url | http://dx.doi.org/10.1155/2015/834085 |
work_keys_str_mv | AT juneuipark dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT jinahjang dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT jihyechoi dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT misunkang dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT yunjuwoo dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT youngrimseong dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT chanbumchoi dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT hyesoonlee dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT sangcheolbae dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice AT yongsoobae dcbasedimmunotherapycombinedwithlowdosemethotrexateeffectiveinthetreatmentofadvancedciainmice |