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.
Conclusion: 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.
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