T cells in Chronic Pelvic Pain

描述（由申请人提供）：慢性盆腔疼痛是慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS）患者的标志，这是一种前列腺炎，是美国男性发病率的重要来源。长期以来，CP/CPPS的微生物病因学一直被假设，但由于该综合征的慢性性质、经常延迟诊断以及健康男性前列腺中细菌的混杂存在，很难证明因果关系。我们最近从一个慢性骨盆疼痛的病人身上发现了一种临床大肠杆菌菌株，命名为CP1，它能够忠实地复制慢性疼痛

DESCRIPTION (provided by applicant): Chronic pelvic pain is the hallmark of patients with Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a category of prostatitis that is a significant source of morbidity in American men. A microbial etiology for CP/CPPS has long been postulated but a cause and effect relationship has been difficult to demonstrate due to the chronic nature of the syndrome, the often-delayed diagnosis, and the confounding presence of bacteria in prostates of healthy men. We recently identified a clinical E. coli strain named CP1 from a patient with chronic pelvic pain that was capable of faithfully replicating the chronic pain state in a mouse model of bacterial prostatitis. The CP1 strain infected the prostate of NOD and B6 mice, resulting in an inflammatory response in both strains but inducing the chronic pain state only in NOD mice. Chronic pain persisted even in the absence of detectable bacterial colonization. Our preliminary studies show that the pain is transferable using CD4+ T cells and is associated with a predominant Th1/Th17 immune response. In contrast, CP1 infection in the non-pain permissible B6 mice induced CD4 T cells with an IL-4 response and elevated levels of FoxP3+ CD25+ regulatory T cells. Infection with NU14, a non-pain inducing E. coli strain also resulted in elevated levels of FoxP3+ CD25+ regulatory T cells in both the NOD and B6 mice, suggesting an association between the presence of regulatory T cells and absence of pelvic pain. These studies lead us to hypothesize that bacterial-induced chronic pelvic pain is mediated by IFN-¿ and IL-17 secreting CD4+ T cells and suppressed by regulatory T cells in the prostate. We will address our hypothesis using the following specific aims: 1. identifying the functional role of Th1/Th17 T cells in chronic pelvic pain. 2. Defining the mechanism of T cell trafficking to the injured prostate. 3. Identifying strategies to promote self-tolerance in the prostate. These studies are expected to result in an understanding of specific mechanisms of chronic pelvic pain in CPPS as well as identification of novel methodologies to effect pain reduction and disease resolution in CPPS patients.