title: Combination with methotrexate and cyclophosphamide attenuated maturation of dendritic cells: inducing Treg skewing and Th17 suppression in vivo.
abstract: 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.
authors.affiliation: Department of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wu Yi Road, Taiyuan 030001, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Yu
authors.forename: Caihong
authors.initials: C
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Xiangcong
authors.initials: X
authors.lastname: Zhao
authors.forename: Lixing
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D003520:Cyclophosphamide; D010047:Ovalbumin; D008727:Methotrexate