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Measurement of Tactile Allodynia in a Murine Model of Bacterial Prostatitis
Published on: January 16, 2013
An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic
Yafei Hou1, Jason DeVoss, Vinh Dao
1Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California 94143, USA.
Abstract:
Chronic prostatitis is a common disease of unclear etiology and has no specific treatment. Mice deficient in the expression of the autoimmune regulator (Aire) gene, which are defective in thymic expression of self antigens and central tolerance, develop spontaneous prostatitis. In this study, we found that Aire-deficient mice developed spontaneous B and T cell immune responses to a prostate autoantigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be novel. We show that thymic expression of this self antigen was Aire dependent. Moreover, prostatitis was induced in WT mice through immunization with SVS2, demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The clinical relevance of this antigen was highlighted by our observation that patients with chronic prostatitis possessed specific autoantibodies against the human SVS2-like seminal vesicle protein semenogelin. These results provide direct evidence that spontaneous chronic prostatitis is an autoimmune disease and is regulated by both central and peripheral tolerance. Moreover, SVS2 and semenogelin are among the relevant autoantigens in mice and humans, respectively.
Insights
Chronic prostatitis may be an autoimmune disease. Researchers found that immune responses to prostate autoantigen SVS2 can cause prostatitis, with relevance in human patients lacking autoimmune regulator (Aire) gene function.
Area of Science:
- Immunology
- Urology
- Autoimmunity
Background:
- Chronic prostatitis is a prevalent condition with unknown causes and limited treatment options.
- Mice lacking the autoimmune regulator (Aire) gene exhibit defective central tolerance and develop spontaneous prostatitis.
- The autoimmune regulator (Aire) is crucial for maintaining self-tolerance by controlling the expression of self-antigens in the thymus.
Purpose of the Study:
- To investigate the role of autoimmune regulator (Aire) gene deficiency in the development of chronic prostatitis.
- To identify specific prostate autoantigens involved in Aire-dependent prostatitis.
- To explore the clinical relevance of identified autoantigens in human chronic prostatitis patients.
Main Methods:
- Utilized Aire-deficient mice to study spontaneous prostatitis development.
- Assessed B and T cell immune responses to seminal vesicle secretory protein 2 (SVS2) in Aire-deficient mice.
- Induced prostatitis in wild-type (WT) mice by immunizing with SVS2.
- Analyzed autoantibodies against human semenogelin in patients with chronic prostatitis.
Main Results:
- Aire-deficient mice developed spontaneous immune responses against SVS2, a novel prostate autoantigen.
- Thymic expression of SVS2 was dependent on the autoimmune regulator (Aire) gene.
- Immunization with SVS2 successfully induced prostatitis in WT mice.
- Patients with chronic prostatitis showed specific autoantibodies to semenogelin, a human homolog of SVS2.
Conclusions:
- Spontaneous chronic prostatitis is an autoimmune disease regulated by central and peripheral tolerance mechanisms.
- The autoimmune regulator (Aire) plays a critical role in preventing autoimmune responses to prostate autoantigens.
- SVS2 and semenogelin are identified as relevant autoantigens in murine and human prostatitis, respectively.
