title: DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice.
abstract: 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).
authors.affiliation: JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
authors.forename: Jun-Eui
authors.initials: JE
authors.lastname: Park
authors.affiliation: JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
authors.forename: Jinah
authors.initials: J
authors.lastname: Jang
authors.affiliation: JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Choi
authors.affiliation: JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Kang
authors.affiliation: JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Woo
authors.affiliation: JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
authors.forename: Young-Rim
authors.initials: YR
authors.lastname: Seong
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Republic of Korea.
authors.forename: Chan-Bum
authors.initials: CB
authors.lastname: Choi
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Republic of Korea.
authors.forename: Hye-Soon
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.affiliation: JW CreaGene Research Institute, JW CreaGene Inc., Seongnam-si, Gyeonggi-do 462-120, Republic of Korea ; Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016219:Immunotherapy, Adoptive; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D008727:Methotrexate