title: Functional Mechanism(s) of the Inhibition of Disease Progression by Combination Treatment with Fingolimod Plus Pathogenic Antigen in a Glucose-6-phosphate Isomerase Peptide-Induced Arthritis Mouse Model.
abstract: We previously reported that combination treatment with fingolimod (FTY720) plus antigenic peptide of glucose-6-phosphate isomerase (residues 325-339) (GPI325-339) from the onset of symptoms significantly inhibited disease progression in a mouse model of GPI325-339-induced arthritis. In this study, we investigated the mechanism(s) involved. The model mice were treated from arthritis onset with FTY720 alone, GPI325-339 alone, or the combination of FTY720 plus GPI325-339. At the end of treatment, inguinal lymph nodes (LNs) were excised and examined histologically and in flow cytometry. Levels of apoptotic cells, programmed death-1-expressing CD4(+)forkhead box P3(-) nonregulatory T cells (non-Tregs), and cytotoxic T-lymphocyte antigen 4-expressing non-Tregs in inguinal LNs were markedly increased in the combination treatment group mice. Regulatory T cells (Tregs) were also increased. These results indicate that combination treatment with FTY720 plus GPI325-339 inhibits the progression of arthritis by inducing clonal deletion and anergy of pathogenic T cells and also by immune suppression via Tregs.
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Norihisa
authors.initials: N
authors.lastname: Mikami
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Fumiya
authors.initials: F
authors.lastname: Otani
authors.forename: Mai
authors.initials: M
authors.lastname: Miyawaki
authors.forename: Miku
authors.initials: M
authors.lastname: Takatsuji
authors.forename: Rie
authors.initials: R
authors.lastname: Banno
authors.forename: Takumi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Fujita
authors.forename: Kazutake
authors.initials: K
authors.lastname: Tsujikawa
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D018450:Disease Progression; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008811:Mice, Inbred DBA; D010455:Peptides / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D000941:Antigens; D007166:Immunosuppressive Agents; D010455:Peptides; D005956:Glucose-6-Phosphate Isomerase; D000068876:Fingolimod Hydrochloride