title: Reduction of the incidence and severity of collagen-induced arthritis by constitutive Nur77 expression in the T cell lineage.
abstract: OBJECTIVE
  To test the hypothesis that constitutive expression of Nur77 in the T cell lineage will suppress the development and pathogenesis of collagen-induced arthritis (CIA) and to understand the mechanisms by which Nur77 overexpression influences the arthritogenic response to type II collagen (CII).
  
  
  METHODS
  Nur77-transgenic and wild-type C57BL/6 mice were immunized with CII and were monitored for the development and severity of arthritis. Pathologic changes were examined by histology and radiography. The effects of Nur77 overexpression on immune responses were evaluated by cytokine production in vitro and serum levels of CII-specific antibodies. Sensitivity of T cells to apoptosis induction was analyzed in vitro following stimulation with anti-CD3 monoclonal antibody or glucocorticoid.
  
  
  RESULTS
  The incidence and severity of CIA was significantly decreased in Nur77-transgenic mice compared with wild-type controls. Attenuation of the disease was associated with increased apoptosis induction in transgenic T cells and decreased production of CII-specific IgG2a antibodies in transgenic mice. Overexpression of Nur77 in the T cell compartment did not affect Th1/Th2 cytokine production or balance.
  
  
  CONCLUSIONS
  Nur77 overexpression in the T cell lineage attenuates the development and progression of CIA, probably by promoting activation-induced T cell apoptosis and by inhibiting CII-specific antibody production.
authors.affiliation: Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Swanthri
authors.initials: S
authors.lastname: De Silva
authors.forename: Shuhua
authors.initials: S
authors.lastname: Han
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.forename: David P
authors.initials: DP
authors.lastname: Huston
authors.forename: Astar
authors.initials: A
authors.lastname: Winoto
authors.forename: Biao
authors.initials: B
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000917:Antibody Formation; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D002460:Cell Line; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D024043:Collagen Type II; D016207:Cytokines; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors