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...

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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/834085
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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).
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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
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