Non-obese Diabetic (NOD) Mice are Genetically Susceptible to Experimental Autoimmune Prostatitis (EAP)

Rivero, Virginia; Cailleau, Catherine; Depiante-Depaoli, M; Riera, Clelia M.; Carnaud, Claude

doi:10.1006/jaut.1998.0248

Cited by 65 publications

(89 citation statements)

References 35 publications

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“…As adults, the NMS mice display significant perigenital mechanical allodynia, as well as evidence of mast cell degranulation in prostate tissue. The use of NMS is a novel approach to developing a preclinical model of CP/CPPS in that it replicates the early life stress that is often reported by patients with chronic pelvic pain [12][13][14] , as well as incorporating a non-invasive induction, as opposed to more commonly used, chemically-and immunologically-induced inflammation of the prostate 34,[36][37][38][39] . Furthermore, NMS in mice has been shown to produce comorbid symptomology, including altered anxiety-like and anhedonic behaviors, increased micturition rates, and hindpaw hypersensitivity ( 16 ; data not shown), similar to the comorbid somatic, mood, and visceral disorders exhibited by CP/CPPS patients [4][5][6] .…”

Section: Discussionmentioning

confidence: 99%

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

Fuentes

Pierce

O’Neil

et al. 2015

JoVE

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a lifetime prevalence of 14% and is the most common urological diagnosis for men under the age of 50, yet it is the least understood and studied chronic pelvic pain disorder. A significant subset of patients with chronic pelvic pain report having experienced early life stress or abuse, which can markedly affect the functioning and regulation of the hypothalamicpituitary-adrenal (HPA) axis. Mast cell activation, which has been shown to be increased in both urine and expressed prostatic secretions of CP/ CPPS patients, is partially regulated by downstream activation of the HPA axis. Neonatal maternal separation (NMS) has been used for over two decades to study the outcomes of early life stress in rodent models, including changes in the HPA axis and visceral sensitivity. Here we provide a detailed protocol for using NMS as a preclinical model of CP/CPPS in male C57BL/6 mice. We describe the methodology for performing NMS, assessing perigenital mechanical allodynia, and histological evidence of mast cell activation. We also provide evidence that early psychological stress can have long-lasting effects on the male urogenital system in mice. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

Fuentes

Pierce

O’Neil

et al. 2015

JoVE

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“…Our laboratory has pioneered the development of animal models of experimental autoimmune prostatitis (EAP), which is achieved by immunization of animals with prostate Ags plus adjuvant. These models show almost all previously mentioned characteristics of human disease: the presence of IFN-g-secreting lymphocytes specific to prostate Ags, increased levels of cytokines in semen, pelvic pain, inflammation, and the type of infiltration and histological lesions seen in the target organ (13)(14)(15)(16). Studies focused on differential susceptibility to the development of EAP have shown that NOD, C57BL/6, SJL, A⁄J, and BALB/c mice exhibited different severity of prostatic inflammation after EAP induction, with NOD and BALB/c mice the most susceptible and the most resistant strains, respectively (4,13,17).…”

mentioning

confidence: 87%

“…Studies focused on differential susceptibility to the development of EAP have shown that NOD, C57BL/6, SJL, A⁄J, and BALB/c mice exhibited different severity of prostatic inflammation after EAP induction, with NOD and BALB/c mice the most susceptible and the most resistant strains, respectively (4,13,17). 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).…”

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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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“…The observation of muscle and peripheral nerve autoimmunity is not unexpected if one considers that, beyond spontaneously developing T1D, NOD mice are susceptible to many other autoimmune diseases. These include autoimmune sialadenitis [30], autoimmune thyroiditis [31], hemolytic anemia [32], and prostatitis in male mice [33]. Accordingly, the NODderived mouse has been considered as a model of primary Sjogren syndrome, Guillain-Barré syndrome and multiple sclerosis [34][35][36].…”

Section: Cd25mentioning

confidence: 99%

Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system

et al. 2010

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NOD mice spontaneously develop insulin-dependent diabetes around 10-40 wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward b cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS À/À and ICOSL À/À NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro-muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4 1 and CD8 1T cells from diseased donors to naïve NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS À/À NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS À/À NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells.

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Non-obese Diabetic (NOD) Mice are Genetically Susceptible to Experimental Autoimmune Prostatitis (EAP)

Cited by 65 publications

References 35 publications

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

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

Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system

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