Causes and consequences of chronic inflammation of the prostate: from human disease to animal models and viceversa

MOTRICH, RUBEN D.

Mar del Plata

Congreso; LXVI Reunión Anual de SAI, LXIII Reunión Anual de la SAIC, Reunión Anual de la SAFIS, IX Reunión Anual de la NANOMEDAR, Reunión Anual de la SAV.; 2018

Sociedad Argentina de Inmunologia, Sociedad Argentina de Investigacion Clinica

The prostate is the target of disorders that affect men of all ages. Pathologies range from infection, to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), to benign hyperplasia and cancer. CP/CPPS is a prevalent disease affecting men younger than 50 years and characterized by pelvic pain and chronic inflammation of the prostate of unknown etiology. Autoimmune responses against prostate antigens were revealed in CP/CPPS patients. In fact, self-reactivity of Th1 cells to prostate and seminal plasma proteins were detected in a considerable proportion of patients in the absence of infection, suggesting a Th1 autoimmune response as the underlying disease mechanism. These autoimmune responses were associated with elevated levels of inflammatory cytokines and chemokines, and leukocyte subpopulations in semen. Interestingly, striking alterations in the semen quality of these patients were also reported. Besides, rodent models of experimental autoimmune prostatitis (EAP) have allowed an important advance in the understanding of human disease. Different susceptibilities to the induction of EAP were observed among mouse strains. NOD mice were the most susceptible to the induction of EAP when compared to C57BL/6 or BALB/c mice. After immunization, NOD mice developed specific Th1/Th17 cell-mediated responses that caused severe histopathology in the prostate and the induction of chronic pelvic pain. In fact, INFγ has shown to be critical to confer pathogenic T cells the capability of homing to the prostate, where they induced leukocyte recruitment and also pelvic pain development. Besides, Treg have been shown to be critical during the inductive phase of EAP. Indeed, Treg-depletion made resistant mice vulnerable to EAP development by significantly increasing pathogenic Th1 cells. Altogether, our results support the notion that an autoimmune response to prostate antigens may be the underlying cause of CP/CPPS. Th1 cells induce local inflammation and pelvic pain development, thus emerging as a putative therapeutic target in CP/CPPS patients.