Lymph node transplantation decreases swelling and restores immune responses in a transgenic model of lymphedema

Introduction: Secondary lymphedema is a common complication of cancer treatment and recent studies have demonstrated that lymph node transplantation (LNT) can decrease swelling, as well as the incidence of infections. However, although these results are exciting, the mechanisms by which LNT improves these pathologic findings of lymphedema remain unknown. Using a transgenic mouse model of lymphedema, this study sought to analyze the effect of LNT on lymphatic regeneration and T cell-mediated immune responses. Methods: We used a mouse model in which the expression of the human diphtheria toxin receptor is driven by the FLT4 promoter to enable the local ablation of the lymphatic system through subdermal hindlimb diphtheria toxin injections. Popliteal lymph node dissection was subsequently performed after a two-week recovery period, followed by either orthotopic LNT or sham surgery after an additional two weeks. Hindlimb swelling, lymphatic vessel regeneration, immune cell trafficking, an...引言：继发性淋巴水肿（secondary lymphedema）是癌症治疗的常见并发症，近期研究已证实，淋巴结移植（Lymph node transplantation, LNT）可减轻肿胀，同时降低感染发生率。尽管上述研究结果令人振奋，但淋巴结移植改善淋巴水肿病理表现的具体机制仍不明晰。本研究利用淋巴水肿转基因小鼠模型（transgenic mouse model of lymphedema），旨在分析淋巴结移植对淋巴管再生以及T细胞介导免疫应答（T cell-mediated immune responses）的影响。 方法：本研究采用由FLT4启动子（FLT4 promoter）驱动人白喉毒素受体（human diphtheria toxin receptor）表达的小鼠模型，可通过后肢皮下注射白喉毒素实现淋巴系统的局部消融。待恢复两周后，实施腘窝淋巴结清扫术（popliteal lymph node dissection），再经过额外两周的恢复期后，分别开展原位淋巴结移植或假手术（sham surgery）处理。后续将对后肢肿胀程度、淋巴管再生情况、免疫细胞迁移以及……