AR信号通路对良性前列腺增生组织中CD4+T淋巴细胞浸润和功能的影响及分子机制

良性前列腺增生(BPH)是老年男性常见疾病。新近研究表明，免疫炎症反应参与BPH发生发展。我们前期研究发现，不同雄激素状态下CD4+T细胞浸润状态不同；CD4+T细胞可促进BPH前列腺细胞增殖。因而假设，在雄激素受体(AR)信号通路调控下，CD4+T细胞与前列腺细胞相互作用促进BPH发生发展。本课题拟：⑴研究抗雄激素药物对BPH患者前列腺组织内CD4+T细胞浸润和活化的影响，及与前列腺细胞增殖/凋亡的关系；⑵在AR前列腺特异性敲除小鼠模型中，研究AR信号通路对CD4+T细胞浸润和功能的影响；⑶利用我们已经建立的原代人BPH前列腺上皮和间质细胞，通过敲除和过表达前列腺细胞的AR，分别与CD4+T细胞共培养，观察前列腺细胞对CD4+T细胞趋化和功能的影响，以及CD4+T细胞对前列腺细胞增殖/凋亡的影响。本研究拟在不同层面阐明AR信号通路调控免疫炎症反应影响BPH发生发展的细胞和分子生物学机制。

Benign prostatic hyperplasia (BPH) is one of the most common diseases in aging men, but the underlying mechanism is far from completely understood. CD4+ T lymphocyte is the inflammatory cell type of the most commonly found in BPH prostatic tissue. In the preliminary experiment, we found that BPH prostatic cell had chemotactic effect on CD4+ T lymphocytes and CD4+ T lymphocytes stimulated prostatic cell proliferation. Therefore, we hypothesized that under androgen receptor(AR) regulation the interaction between prostate cells and CD4+ T lymphocytes was involved in the development and progression of BPH. In this project, we will: ⑴in BPH patients, study the influence of androgen inhibition therapy on the CD4+ T lymphocytes infiltration and functional status in prostate tissues; ⑵in the mice model lacking epithelial AR or stromal AR within the prostate, observe the changes of CD4+ T lymphocytes infiltration and functional status in the prostate; ⑶in the co-culture system, study the interaction between prostate cells and CD4+ T lymphocytes. At the same time, by knocking-in and knocking-out of AR in prostate cells, we examine the influence of AR signaling on the interaction of prostate cells and CD4+ T lymphocytes.