T cells in Chronic Pelvic Pain

T 细胞在慢性盆腔疼痛中的作用

基本信息

批准号：
8438510
负责人：
PRAVEEN THUMBIKAT
金额：
$ 33.6万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8438510
关键词：
Address Adoptive Cell Transfers Adoptive Transfer Affect American Animals Anogenital region Antigen Targeting Antigens Autoimmune Process Bacteria Bacterial Infections Bacterial Prostatitis Biological Assay C57BL/6 Mouse CD4 Positive T Lymphocytes CD8B1 gene Categories Chronic Chronic Prostatitis Clinic Clinical Coculture Techniques Diagnosis Disease Dysuria Escherichia coli Etiology Exhibits Future Human IL2RA gene Immune Sera Immune response Immunotherapy In Vitro Inbred NOD Mice Infection Inflammatory Response Interferons Interleukin-17 Interleukin-4 Lead Massage Mediating Medical Methodology Methods Modeling Morbidity - disease rate Mus Names Nature Pain Patients Pelvic Pain Peripheral Blood Mononuclear Cell Phenotype Prostate Prostatic Recruitment Activity Regulatory T-Lymphocyte Resolution Role Self Tolerance Self-Injurious Behavior Serum Source Symptoms Syndrome T cell response T-Lymphocyte Testing Testis United States United States National Institutes of Health Urine chemokine chronic pain chronic pelvic pain injured macrophage mast cell men microbial mouse model neutrophil novel penis peripheral blood prostatitis public health relevance receptor response secondary infection trafficking

项目摘要

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.

描述（由适用提供）：慢性骨盆疼痛是患有慢性前列腺炎/慢性骨盆疼痛综合征（CP/CPPS）的患者的标志，这是美国男性发病率的重要来源的类别。长期以来一直假定了CP/CPP的微生物病因，但是由于综合征的慢性性质，经常延迟的诊断性以及在健康男性前列腺中细菌的混淆，因此很难证明其因果关系。我们最近从患有慢性骨盆疼痛患者的患者中鉴定出一种名为CP1的临床大肠杆菌菌株，能够忠实地复制慢性疼痛 CP1菌株感染了NOD和B6小鼠的前列腺，导致两种菌株的炎症反应，但仅诱导NOD小鼠的慢性疼痛状态。即使没有可检测到的细菌定植，慢性疼痛也持续存在。我们的初步研究表明，疼痛是使用CD4+ T细胞转移的，并且与主要的TH1/TH17免疫响应有关。相反，非pain允许B6小鼠中的CP1感染诱导CD4 T细胞具有IL-4反应和FOXP3+ CD25+调节性T细胞的水平升高。在NU14中感染了NU14，非吸毒诱导的大肠杆菌菌株也导致NOD和B6小鼠的FOXP3+ CD25+调节性T细胞的水平升高，这表明调节性T细胞的存在与不存在骨盆疼痛之间存在关联。这些研究使我们假设细菌诱导的慢性骨盆疼痛是由IFN-€和IL-17分泌CD4+ T细胞介导的，并被前列腺中的调节性T细胞抑制。我们将使用以下特定目的来解决我们的假设：1。确定Th1/Th17 T细胞在慢性骨盆疼痛中的功能作用。 2。将T细胞运输的机理定义为受伤的前列腺。 3.确定促进前列腺自我耐受性的策略。预计这些研究将导致了解CPP中慢性骨盆疼痛的特定机制，并鉴定出新的方法来减轻CPP患者的疼痛和疾病分辨率。