Combination with Methotrexate and Cyclophosphamide Attenuated Maturation of Dendritic Cells: Inducing Treg Skewing and Th17 Suppression In Vivo

Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4+T cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs),...

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Bibliographic Details
Published in:Clinical & developmental immunology 2013-01, Vol.2013 (2013), p.1-12
Main Authors: Wang, Lixing, Zhao, Xiangcong, Luo, Jing, Wang, Caihong, Yu, Xiaoyang, Li, Xiaofeng
Format: Article
Language:English
Subjects:
Animals
Antigen-presenting cells
Antigens, Surface - metabolism
Autoimmune diseases
Bone marrow
Cell Differentiation - drug effects
Cyclophosphamide - pharmacology
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Immune system
Immunology
Immunophenotyping
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Male
Methotrexate - pharmacology
Mice
Ovalbumin - immunology
Phenotype
T-Lymphocytes, Regulatory - drug effects
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
Th17 Cells - drug effects
Th17 Cells - immunology
Th17 Cells - metabolism
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Summary:Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4+T cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs), which are the most powerful antigen-presenting cells, play an important role in regulating the balance of Th17 and Treg. The combination of disease modifying antirheumatic drugs (DMARDs) is an important strategy of RA therapy. In this study, we investigated the effect of MTX and CTX on DC maturation in ovalbumin (OVA) immunized mice. Th17 inflammatory response is stronger, while the level of DCs maturity is higher. In contrast, the immunosuppression of Treg is stronger. We found that MTX combined with CTX significantly inhibited the DCs maturity and downregulated the antigen presenting capacity of DCs. As a result, it reestablished a balance of Th17 and Treg. Our study adds a novel mechanism and therapeutic target of MTX combined with CTX for autoimmune disease treatment.
ISSN:2314-8861
1740-2522
2314-7156
1740-2530
DOI:10.1155/2013/238035