Lymphotoxin β receptor signaling is required for inflammatory lymphangiogenesis in the thyroid
Lymphotoxin β receptor signaling is required for inflammatory lymphangiogenesis in the thyroid
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DOI：
10.1073/pnas.0606697104
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发表时间：
2007-03-20
影响因子：
11.1
通讯作者：
Lira, Sergio A.
中科院分区：
文献类型：
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作者：
Furtado, Glaucia C.;Marinkovic, Tatjana;Lira, Sergio A.
淋巴细胞浸润到甲状腺并形成淋巴结样结构是桥本甲状腺炎的标志。在这里，我们证明了淋巴管存在于这些浸润。在甲状腺中过度表达趋化因子CCL 21的小鼠（TGCCL 21小鼠）出现了类似的淋巴浸润和淋巴管。与对照组相比，缺乏成熟T和B细胞的TGCCL 21小鼠（RAGTGCCL 21小鼠）没有细胞浸润或淋巴管数量增加。将CD 3（+）CD 4（+）T细胞转移到RAGTGCCL 21小鼠中促进了甲状腺中LYVE-1（+）podoplanin（+）Prox-1（+）血管的发育。甲状腺光敏素β受体或甲状腺光敏素a的基因缺失可消除甲状腺炎症区域淋巴管的发育，但不影响邻近淋巴管的发育。这些结果为研究甲状腺炎性淋巴管生成提供了一个模型，并暗示了这一过程中的光毒素β受体信号传导。
Infiltration of lymphocytes into the thyroid gland and formation of lymph node-like structures is a hallmark of Hashimoto's thyroiditis. Here we demonstrate that lymphatic vessels are present within these infiltrates. Mice overexpressing the chemokine CCL21 in the thyroid (TGCCL21 mice) developed similar lymphoid infiltrates and lymphatic vessels. TGCCL21 mice lacking mature T and B cells (RAGTGCCL21 mice) did not have cellular infiltrates or increased number of lymphatic vessels compared with controls. Transfer of CD3(+)CD4(+) T cells into RAGTGCCL21 mice promoted the development of LYVE-1(+)podoplanin(+)Prox-1(+) vessels in the thyroid. Genetic deletion of lymphotoxin beta receptor or lymphotoxin a abrogated development of lymphatic vessels in the inflamed areas in the thyroid but did not affect development of neighboring lymphatics. These results define a model for the study of inflammatory lymphangiogenesis in the thyroid and implicate lymphotoxin beta receptor signaling in this process.