新生淋巴管和异位类淋巴结——肾脏纤维化干预的新靶点？

如何抑制慢性肾脏病（CKD）肾脏纤维化的进展，是全世界肾脏病工作者面临的难题。近年来研究发现，肾脏炎症性巨噬细胞在肾脏炎症损伤和肾纤维化进展中起核心作用，但其机制尚不明了。我们在450例肾穿组织标本中发现，CKD患者肾脏纤维化区域巨噬细胞浸润伴有淋巴管新生和异位类淋巴结形成。新生淋巴管密度与肾间质纤维化程度、浸润的炎症细胞以及类淋巴结的密度显著相关。结合最新研究以及本课题组前期研究，我们提出假说：炎症性巨噬细胞在肾脏病变微环境来源的VEGF-C的作用下生成淋巴管，但新生淋巴管引流功能缺陷，导致通过其转运的炎症细胞在原位聚集形成异位类淋巴结，导致慢性炎症的维持和肾脏纤维化的进展。我们建立动物模型，进一步明确淋巴管新生、转运能力缺陷以及异位类淋巴结结构形成的确切机制，寻找促进新生淋巴管引流功能成熟，清除异位类淋巴结有效措施，从而为肾脏纤维化的治疗提供新的策略。

The progression of renal interstitial fibrosis in CKD is a tough challenge for the whole world, and a radical cure for this condition has not yet been established.The current study suggest the number of interstitial inflammatory macrophages increase markedly and triggers a cascade of events leading to the development of fibrosis and the loss of renal cells.However, their details remain unclear.We found that macrophages infiltrated with the lymphangiogenesis and tertiary lymphoid neogenesis in renal interstitium in about 450 biopsies. The density of newly formed lymphatic vessel inversely correlated with the severity of tubular lesions and interstitial fibrosis It was also significantly associated with the amount of infiltrating macrophages, dendritic cells, lymphocytes and tertiary lymphoid tissues.According to the recent research and our job,we suppose that inflammatory macrophages contribute to lymphangiogenesis depending on the VEGF-C derived from the renal lesion microenvironment. The newly formed immature lymphatic vessels are not able to carry the infiltrated immune cells to the draining lymph node. We believe that such a relative defect in the lymphatic drainage of the inflamed tissue is a trigger for the cascade of events leading to the development of tertiary lymphoid neogenesis which maintain chronic inflammatory disorders. In the future,we will perform a animal model to identify the detailed mechanism of lymphangiogenesis and tertiary lymphoid neogenesis.Our destination is to promote the lymphatic vessels drainining more infiltrated immune cells and finally diminish or elicit tertiary lymphoid tissues. Thus there will be a new strategy to weaken the chronic inflammation and renal fibrosis.