Chronic non-bacterial inflammation of the prostate is associated with multiple prostate diseases including chronic prostatitis-chronic pelvic pain syndrome (CP-CPPS), benign prostatic hyperplasia (BPH), and prostate cancer. CP-CPPS is disease of pelvic pain symptoms that affects men of any age and it is estimated that 50% of men experience the disorder during their lifetime. According to the National Institutes of Health, prostatitis accounts for 25% of all office visits involving the genitourinary system by young and middle-aged men. Similarly, chronic non-bacterial inflammation is virtually always present in BPH tissue. The chronic inflammatory processes in BPH are linked to hyperplasia and may be associated with tissue remodeling resulting in adenoma formation. Inflammation also is linked to prostate cancer. To address the problem of prostate inflammation a novel genetically modified mouse model was developed. The model, which expresses a model antigen on prostate epithelial cells provides the tools needed to probe factors linked to initiation and regulation of prostate inflammation. Preliminary data demonstrate the utility of the model and have identified several factors important to the development of inflammation and its regulation. These data provide a basis for the hypothesis that a Type I response initiates prostate inflammation, which expands to include T cells reactive with multiple prostate antigens. Further, inflammation is regulated by both MDSC and Treg. To address this hypothesis, three specific aims are proposed: Aim 1. Initiation and maintenance of chronic autoimmune prostate inflammation, Aim 2. Role of myeloid-derived suppressor cells in controlling acute inflammation and modulating regulatory T cells and Aim 3. Role of Myeloid-derived suppressor cells in the regulation of chronic autoimmune prostate inflammation. Pursuit of the proposed studies will provide novel information on the factors linked to initiation and control of prostate inflammation. PUBLIC HEALTH RELEVANCE: Chronic non-bacterial inflammation of the prostate is associated with multiple prostate diseases including chronic prostatitis-chronic pelvic pain syndrome, benign prostatic hyperplasia, and prostate cancer. The links between inflammation and prostate cancer are gaining acceptance. Therefore, it is of importance to define the parameters necessary for controlling non-bacterial chronic prostate inflammation.