title: Decoy receptor 3 attenuates collagen-induced arthritis by modulating T cell activation and B cell expansion.
abstract: OBJECTIVE
  To investigate the immune-modulated effects of decoy receptor 3 (DCR3) in an experimental model of rheumatoid arthritis (RA).
  
  
  METHODS
  We delivered DCR3 plasmid into collagen-induced arthritis (CIA) mice using the hydrodynamic method and evaluated the serum level of DCR3 protein by ELISA. After immunization, we assessed disease severity of arthritis incidence, arthritis scores, paw thickness, and means of arthritic limbs, and used hematoxylin and eosin staining to observe synovial hyperplasia. We analyzed numbers of murine splenocytes and inguinal lymphocyte cells, cell populations, and serum proinflammatory cytokines by flow cytometry. We investigated B cell proliferation by carboxyfluorescein succinimidyl ester assay. We evaluated serum levels of total IgG2a and type II collagen-specific IgG and IgG2a using ELISA.
  
  
  RESULTS
  DCR3 expression in sera significantly attenuated disease severity in CIA mice. We found that DCR3 inhibited the volume of inguinal lymph nodes, numbers of CD19+ B cells, and populations of interferon-γ, interleukin 4 (IL-4), IL-17A, and Foxp3-producing CD4+ T cell in vivo. We found that DCR3 inhibited Pam3CSK4 (Toll-like receptor 1/2 ligand)-induced B220+ B cell proliferation in vitro. DCR3 treatment reduced the serum level of IL-6, total IgG2a, and CII-specific IgG2a antibody.
  
  
  CONCLUSIONS
  We postulated that the protective effects of DCR3 in CIA resulted from modulation of the immune system by maintaining the B/T cell balance and decreasing lymphocyte expansion. We suggest DCR3 as a prophylactic and potential therapeutic agent in the treatment of RA.
authors: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors: Chia-Pi
authors: CP
authors: Cheng
authors: Huey-Kang
authors: HK
authors: Sytwu
authors: Deh-Ming
authors: DM
authors: Chang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D024043:Collagen Type II / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II; D016207:Cytokines; D007074:Immunoglobulin G; D053323:Receptors, Tumor Necrosis Factor, Member 6b