Crucial Role of Interferon-γ in Experimental Autoimmune Prostatitis

Motrich, Rubén Darío; Etten, Evelyne van; Baeke, Femke; Riera, Clelia M.; Mathieu, Chantal; Rivero, Virginia

doi:10.1016/j.juro.2009.11.008

Cited by 26 publications

(41 citation statements)

References 29 publications

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“…Indeed, Irf1 regulates a large number of genes critical for innate and adaptive immunity, including several involved in antigen presentation and cytokine production [66]. Irf1 was also shown to contribute to spontaneous systemic autoimmunity in lupus-prone MRL- Fas lpr mice [67] and several organ-specific autoimmune diseases, including type 1 diabetes mellitus [68], autoimmune prostatitis [69] and experimental autoimmune encephalomyelitis [70]. …”

Section: Discussionmentioning

confidence: 99%

Definition of IFN-γ-related pathways critical for chemically-induced systemic autoimmunity

Pollard

Hultman

Toomey

et al. 2012

Journal of Autoimmunity

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IFN-γ is essential for idiopathic and murine mercury-induced systemic autoimmunity (mHgIA), and heterozygous IFN-γ+/− mice also exhibit reduced disease. This suggests that blocking specific IFN-γ-related pathways that may only partially inhibit IFN-γ production or function will also suppress autoimmunity. To test this hypothesis, mice deficient in genes regulating IFN-γ expression (Casp1, Nlrp3, Il12a, Il12b, Stat4) or function (Ifngr1, Irf1) were examined for mHgIA susceptibility. Absence of either Ifngr1 or Irf1 resulted in a striking reduction of disease, while deficiency of genes promoting IFN-γ expression had modest to no effect. Furthermore, both Irf1– and Ifng-deficiency only modestly reduced the expansion of CD44hi and CD44hiCD55lo CD4+ T cells, indicating that they are not absolutely required for T cell activation. Thus, there is substantial redundancy in genes that regulate IFN-γ expression in contrast to those that mediate later signaling events. These findings have implications for the therapeutic targeting of IFN-γ pathways in systemic autoimmunity.

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Section: Discussionmentioning

confidence: 99%

Definition of IFN-γ-related pathways critical for chemically-induced systemic autoimmunity

Pollard

Hultman

Toomey

et al. 2012

Journal of Autoimmunity

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“…Previously, we reported that Th1 cells play a crucial role in EAP (19). However, no conclusive evidence about the role of Th17 cells in autoimmune prostatitis has been reported to date.…”

Section: Specific Th1 and Th17 Cells Are Induced In Mice With Differementioning

confidence: 90%

“…NOD mice develop severe inflammation in the prostate, accompanied by specific T cell-mediated responses that could be assessed by in vitro-specific proliferation and IFN-g production, but not IL-4 secretion (14,18). A crucial role of IFN-g in EAP has been shown because the absence of IFN-g or transcription factors involved in the IFN-g signaling cascade, such as IRF-1 and STAT-1, made mice resistant to EAP induction (14,19). Recently, IL-17 produced by Th17 cells has been recognized as critical for the development Centro de Investigaciones en Bioquímica Clínica e Inmunología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Cór-doba, Córdoba, 5016 Argentina of autoimmune diseases such as rheumatoid arthritis, EAE, and others (20).…”

mentioning

confidence: 99%

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

Breser

Motrich

Sánchez

et al. 2013

The Journal of Immunology

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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 prostate. In contrast, BALB/c mice, as well as NOD-IFN-γ−/−, exhibited only Th17 cells mainly expressing CCR6 that were not capable of infiltrating the prostate gland. Adoptive transfer experiments of T cells from NOD or NOD–IFN-γ−/− 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-γ, T cells from NOD–IFN-γ−/− 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. Additional 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.

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“…12 Treatment alternatives are limited to standard antiinflammatory and pain-alleviating measures, and the actual mechanisms involved are not well-characterized. Several prostanoids, including PGE 2 and PGI 2 , have pain-inducing properties, 1140 and there is an association between chronic pelvic pain and production of the pro-inflammatory cytokines, IL1β, TNF, IL8 and IFNγ, in particular, 1139,1141 but research in this area is still in need of a rational hypothetical background. Given that these conditions are so poorly understood, extremely debilitating and frequently untreatable, they provide a real opportunity for effective future investigations.…”

Section: Sterile Inflammation and Chronic Painmentioning

confidence: 99%

The Immunophysiology of Male Reproduction

Hedger

2015

Knobil and Neill's Physiology of Reproduction

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Crucial Role of Interferon-γ in Experimental Autoimmune Prostatitis

Abstract: Our results argue for a crucial role of interferon-gamma as a key factor in the pathogenesis of the disease. Intense research is promptly required to identify the pathogenic mechanisms underlying chronic prostatitis/chronic pelvic pain syndrome to find a more rational therapy.

Cited by 26 publications

References 29 publications

Definition of IFN-γ-related pathways critical for chemically-induced systemic autoimmunity

Definition of IFN-γ-related pathways critical for chemically-induced systemic autoimmunity

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

The Immunophysiology of Male Reproduction

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