Mediators of vascular inflammation and tertiary lymphoid organ formation in chronic kidney disease

与肾功能正常但其他危险因素相似的个体相比，慢性肾脏疾病（CKD）患者心血管发病率和死亡率增加。慢性炎症可以启动三级淋巴器官（TLO），对肾脏疾病的进展有不同的影响，正如我们在IgA肾病的肾脏炎症队列中所描述的那样。我们之前的研究已经阐明了细胞因子白细胞介素(IL)-17A在CKD中增强血管炎症的机制作用。肾脏和血管炎症通常在已建立的疾病中被诊断出来，因此维持炎症的机制对于CKD患者的治疗成功至关重要。结合临床队列研究和在合作地点建立的特异性基因缺陷小鼠模型，目前的项目旨在1)描述IL-17A在动脉粥样硬化和肾脏TLO形成中的作用，2)fractalkine受体在人类肾脏慢性炎症和CKD小鼠动脉粥样硬化中的作用。这项研究的结果将增强病理生理学的认识，使慢性肾脏疾病患者能够采取特定的抗炎策略

Patients with chronic kidney disease (CKD) suffer from increased cardiovascular morbidity and mortality compared to individuals with normal renal function but otherwise similar risk factors. Chronic inflammation can initiate tertiary lymphoid organs (TLO) with differential effects on kidney disease progression as we have delineated in a cohort with renal inflammation in IgA nephropathy. Our previous investigations have elucidated a mechanistic role of the cytokine interleukin (IL)-17A in enhancing vascular inflammation in CKD. Both, renal and vascular inflammation are usually diagnosed in established disease, thus the mechanisms maintaining inflammation are critical for therapeutic success in patients with CKD. Using a combination of clinical cohort studies and specific gene deficient mouse models established at the collaborating sites, the current project aims at 1) delineating the role of IL-17A in TLO formation in atherosclerosis and the kidney and 2) the role of fractalkine receptor in chronic inflammation in human kidney and murine atherosclerosis in CKD. Results of this study will enhance pathophysiologic understanding to enable specific anti-inflammatory strategies in patients with chronic kidney disease