A critical role for dendritic cells in the formation of lymphatic vessels within tertiary lymphoid structures.

A critical role for dendritic cells in the formation of lymphatic vessels within tertiary lymphoid structures.
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DOI:
10.4049/jimmunol.1004233
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发表时间:
2011-07-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Furtado GC
Furtado GC
中科院分区:
其他
文献类型:
--
作者:
Muniz LR;Pacer ME;Lira SA;Furtado GC

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异位或三级淋巴样聚集体常形成于慢性炎症区。淋巴管,以及高内皮小静脉,在这些淋巴样聚集体中形成,但其发展的机制尚不清楚。在转基因小鼠的甲状腺中,趋化因子CCL21的过度表达导致形成淋巴样聚集体,其中包含拓扑分离的T淋巴细胞和B淋巴细胞、树突状细胞和特化的脉管系统,包括Lyve-1+/Prox-1+淋巴管。在本报告中,我们发现成熟CD4+ T细胞过继转移到ragg缺乏背景下表达CCL21的动物体内,促进宿主NK细胞和DC涌入甲状腺,并在10天内形成新的淋巴管。这一过程依赖于宿主细胞淋巴毒素配体的表达,而不依赖于转移的CD4+ T细胞。消融宿主DC细胞,而非NK细胞,可减少甲状腺新淋巴管的形成。综上所述,这些数据表明CD11c+ DC在诱导三级淋巴样结构的淋巴管生成中起着关键作用。
Ectopic, or tertiary lymphoid aggregates often form in chronically inflamed areas. Lymphatic vessels, as well as high endothelial venules, form within these lymphoid aggregates, but the mechanisms underlying their development is poorly understood. Overexpression of the chemokine CCL21 in the thyroid of transgenic mice leads to formation of lymphoid aggregates containing topologically segregated T and B lymphocytes, dendritic cells and specialized vasculature, including Lyve-1+/Prox-1+ lymphatic vessels. In this report we show that adoptive transfer of mature CD4+ T cells into animals expressing CCL21 in a RAG-deficient background, promotes the influx of host NK cells and DC into the thyroid and the formation of new lymphatic vessels within 10 days. This process is dependent on the expression of lymphotoxin ligands by host cells, but not by the transferred CD4+ T cells. Ablation of host DC, but not NK cells, reduces the formation of new lymphatic vessels the thyroid. Taken together, these data suggest a critical role for CD11c+ DC in the induction of lymphangiogenesis in tertiary lymphoid structures.
树突状细胞对于维持流感病毒感染小鼠肺部的三级淋巴结构至关重要。
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