Lymphatic pumping and lymphatic transport of antigen to lymph node

淋巴泵和淋巴运输抗原至淋巴结

• 批准号: RGPIN-2015-03641
• 负责人: Liao, Shan
• 金额: $ 2.4万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630925
• 关键词: Lymphatic; pumping; lymphatic; transport; antigen

Lymphatic vessels play essential roles in maintaining fluid balance and facilitating immune defense. While the heart beats to drive blood circulation, lymph transport primarily relies on lymphatic vessel pumping. Lymphatic pumping is driven by lymphatic smooth muscle cell (SMC) contraction. The function of lymphatic pumping is to propel lymph and cells transport to the draining lymph node (LN). When antigen and dendritic cells reach the draining lymph node (LN) through afferent lymphatic vessels, they must exit the vessels and migrate deep into the LN to activate T cell responses. However, it is not clear how changes in lymph flow may affect antigen delivery and antigen presentation in LN. In my previous studies, I have developed an intravital imaging model to study lymphatic pumping in mice. Using this model, I demonstrated that nitric oxide (NO) is required to maintain lymphatic pumping in physiological condition via the activation of the endothelial-derived nitric oxide synthase (eNOS). In contrast, the inducible nitric oxide synthase (iNOS) is responsible for the inhibition of lymphatic pumping in oxazolone skin sensitization induced inflammation (OX-inflammation). We hypothesize that NO regulates lymphatic pumping, which consequently modulates lymph flow velocity and flow pattern, and affect antigen delivery in lymph node.

淋巴管在维持液体平衡和促进免疫防御方面发挥着重要作用。心脏跳动推动血液循环，而淋巴液运输主要依靠淋巴管泵送。淋巴泵由淋巴平滑肌细胞 (SMC) 收缩驱动。淋巴泵的功能是推动淋巴液和细胞运输至引流淋巴结 (LN)。当抗原和树突状细胞通过传入淋巴管到达引流淋巴结 (LN) 时，它们必须离开血管并迁移到 LN 深处以激活 T 细胞反应。然而，目前尚不清楚淋巴流的变化如何影响淋巴结中的抗原递送和抗原呈递。在我之前的研究中，我开发了一种活体成像模型来研究小鼠的淋巴泵。使用该模型，我证明一氧化氮 (NO) 是通过激活内皮源性一氧化氮合酶 (eNOS) 来维持生理状态下的淋巴泵所必需的。相反，诱导型一氧化氮合酶 (iNOS) 负责抑制恶唑酮皮肤致敏诱导的炎症（OX 炎症）中的淋巴泵。我们假设 NO 调节淋巴泵，从而调节淋巴流速和流动模式，并影响淋巴结中的抗原递送。