肾脏是肺外结核病中好发的部位之一，但肾结核易在髓质发病的机制还未明确。本研究是我们前期发现并报道泌尿系结核影像特征工作的继续。基于PGE2在肾脏皮、髓质的差异性分布，加上有文献报道高浓度PGE2可由IRAK-M介导免疫抑制，并且，预实验发现高浓度PGE2条件下，单核-巨噬细胞功能受到抑制。本研究在此基础上，探讨高浓度PGE2通过IRAK-M介导的炎症通路受抑在肾结核皮、髓质差异性发病过程中所起的作用。首先，在体外观察高PGE2浓度条件下，IRAK-M对BCG刺激下的单核-巨噬细胞炎症通路及功能的影响；在体内，利用IRAK-M基因敲除(IRAK-M-/-)小鼠，观察肾结核感染过程中高浓度PGE2是否通过IRAK-M介导炎症通路抑制，导致结核在肾皮、髓质的差异性发病。本课题的开展，将完善肾结核的发病机制并解释皮、髓质差异性发病的原因；为抗结核新药研发提供可选择性治疗靶点。

The most common form of extrapulmonary tuberculosis is renal tuberculosis (TB). The renal medulla is the most site invaded by renal TB. However, the contribution of this mechanism is unknown. This study is the continuation of our pre-reported paper about the imaging characteristics of genitourinary TB. Based on the different distribution of prostaglandin E2 (PGE2) between renal cortex and medulla and the low-function of the monocyte-macrophage found at high concentrations of PGE2 in pre-experiment, and in addition, it has been reported the immunosuppression could be mediated by interleukin-1 receptor-associated kinase M (IRAK-M) in high concentration of PGE2, the purpose of our study is to explore the role of IRAK-M which mediates the inhibition of inflammatory pathways in the pathogenesis of different incidence of renal TB between cortex and medulla. First, with the stimulation from BCG and the high concentration of PGE2, the role of IRAK-M in the regulation of inflammatory pathways and the function of the monocyte-macrophage were observed in vitro. Then, the inhibition of inflammatory pathways mediated by IR AK-M which caused the different incidence of renal TB between cortex and medulla was observed in IRAK-M–knockout (IRAK-M–/–) mice. By carrying out this project we hope that the pathogenesis of renal TB and the cause of different incidence between cortex and medulla could be explained. A new therapeutic target could be provided.