Expression of CXCR3 on specific T cells is essential for homing to the prostate gland in an experimental model of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

MARIA LAURA BRESER; RUBEN MOTRICH; LEONARDO SANCHEZ; JUAN PABLO MACKERN-OBERTI; VIRGINIA RIVERO

The Journal of Immunology

The American Association of Immunologists

Año: 2013 vol. 190 p. 3121 - 3133

1550-6606

Experimental autoimmune prostatitis (EAP) is considered a valid model for the human disease chronic prostatitis/chronic pelvic pain syndrome. In this report, we analyzed phenotypic characteristics of T cells that gain access to the prostate and induce leukocyte recruitment in mice with different susceptibility to EAP. After EAP induction, NOD mice developed a specific cellular response characterized by a mixed Th1/Th17 pattern with specific T cells mainly expressing CXCR3 that infiltrated and damaged the pros-tate. In contrast, BALB/c mice, as well as NOD-IFN-g 2 /2, exhibited only Th17 cells mainly expressing CCR6 that were not capableof infiltrating the prostate gland. Adoptive transfer experiments of T cells from NOD or NOD?IFN-g 2 /2 mice to NOD-SCID recipients showed that only T cells from NOD mice successfully infiltrated the prostate. However, after ?in vitro? or ?in vivo? treatment with rIFN- g, T cells from NOD?IFN- g 2 / 2 mice became capable of homing to the prostate and induced leukocyte recruitment. Chemokine levels in prostate tissue from NOD mice showed increased expression levels of CXCR3 ligands. Addi-tional experiments using adoptive transfer of sorted CXCR3+CD3+ T cells or administrating a CXCR3 antagonist treatment confirmed these previous results. Altogether, our results demonstrate that the expression of CXCR3 on effector T cells is essential for their homing to the prostate gland in EAP. CXCR3 emerges as a potential therapeutic target to control chronic prostatitis/chronic pelvic pain syndrome