In allergic airway inflammation, VEGFR-3-mediated lymphangiogenesis occurs in humans and mouse models, yet its immunological roles, particularly in adaptive immunity, are poorly understood. Here, we explored how pro-lymphangiogenic signaling affects the allergic response to house dust mite (HDM). In the acute inflammatory phase, the lungs of mice treated with blocking antibodies against VEGFR-3 (mF4-31C1) displayed less inflammation overall, with dramatically reduced innate and T-cell numbers and reduced inflammatory chemokine levels. However, when inflammation was allowed to resolve and memory recall was induced 2 months later, mice treated with mF4-31C1 as well as VEGF-C/-D knockout models showed exacerbated type 2 memory response to HDM, with increased Th2 cells, eosinophils, type 2 chemokines, and pathological inflammation scores. This was associated with lower CCL21 and decreased T_Regs in the lymph nodes. Together, our data imply that VEGFR-3 activation in allergic airways helps to both initiate the acute inflammatory response and regulate the adaptive (memory) response, possibly in part by shifting the T_Reg/Th2 balance. This introduces new immunomodulatory roles for pro-lymphangiogenic VEGFR-3 signaling in allergic airway inflammation and suggests that airway lymphatics may be a novel target for treating allergic responses.

在过敏性气道炎症中，VEGFR-3 介导的淋巴管生成发生在人类和小鼠模型中，但对其免疫学作用，特别是在适应性免疫中的作用，知之甚少。在这里，我们探讨了促淋巴管生成信号如何影响对屋尘螨 (HDM) 的过敏反应。在急性炎症阶段，用阻断性 VEGFR-3 抗体 (mF4-31C1) 处理的小鼠肺部整体炎症较少，先天细胞和 T 细胞数量显着减少，炎症趋化因子水平降低。然而，当炎症消退并在 2 个月后诱导记忆回忆时，用 mF4-31C1 和 VEGF-C/-D 敲除模型治疗的小鼠表现出对 HDM 的 2 型记忆反应加剧，Th2 细胞、嗜酸性粒细胞、 2 型趋化因子和病理炎症评分。淋巴结中的_{Regs 。}总之，我们的数据表明过敏性气道中的 VEGFR-3 激活有助于启动急性炎症反应和调节适应性（记忆）反应，可能部分是通过改变 T _Reg /Th2 平衡。这引入了促淋巴管生成性 VEGFR-3 信号在过敏性气道炎症中的新免疫调节作用，并表明气道淋巴管可能是治疗过敏反应的新靶点。