Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation
Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation
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DOI：
10.4049/jimmunol.1101854
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发表时间：
2012-04-15
影响因子：
4.4
通讯作者：
Angeli, Veronique
中科院分区：
文献类型：
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作者：
Tan, Kar Wai;Yeo, Kim Pin;Angeli, Veronique
在炎症过程中，免疫细胞在活化的淋巴结（LN）中的积累，加上淋巴细胞出口的短暂关闭，导致细胞急剧扩增。抑制LN扩张的反调节措施必须存在，可能包括重新建立淋巴细胞流出到稳态水平。事实上，我们在小鼠模型中发现，淋巴细胞从淋巴结中的排出在初始滞留后的长期炎症过程中恢复到稳态水平。这种淋巴细胞出口的恢复得到了支持的皮质和髓窦在晚期炎症的优先扩张。在晚期炎症过程中皮质和髓窦重塑依赖于血管内皮生长因子-A分布的时间和空间变化。具体而言，它的表达仅限于在早期炎症的LN的包膜下空间，而其表达集中在皮质旁和髓质区域的LN在后期阶段。我们接下来表明，这一过程主要是由成纤维细胞网状细胞和间质流之间的协同串扰驱动的。我们的数据揭示了LN淋巴管生成在长期炎症过程中的生物学意义，并进一步强调了基质细胞、免疫细胞和间质流在调节LN可塑性和功能中的协同作用。免疫学杂志，2012，188：4065-4080。
During inflammation, accumulation of immune cells in activated lymph nodes (LNs), coupled with a transient shutdown in lymphocyte exit, results in dramatic cellular expansion. Counter-regulatory measures to restrain LN expansion must exist and may include re-establishment of lymphocyte egress to steady-state levels. Indeed, we show in a murine model that egress of lymphocytes from LNs was returned to steady-state levels during prolonged inflammation following initial retention. This restoration in lymphocyte egress was supported by a preferential expansion of cortical and medullary sinuses during late inflammation. Cortical and medullary sinus remodeling during late inflammation was dependent on temporal and spatial changes in vascular endothelial growth factor-A distribution. Specifically, its expression was restricted to the subcapsular space of the LN during early inflammation, whereas its expression was concentrated in the paracortical and medullary regions of the LN at later stages. We next showed that this process was mostly driven by the synergistic cross-talk between fibroblastic reticular cells and interstitial flow. Our data shed new light on the biological significance of LN lymphangiogenesis during prolonged inflammation and further underscore the collaborative roles of stromal cells, immune cells, and interstitial flow in modulating LN plasticity and function. The Journal of Immunology, 2012, 188: 4065-4080.