Neuronal Circuits Modulate Antigen Flow Through Lymph Nodes.
Neuronal Circuits Modulate Antigen Flow Through Lymph Nodes.
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DOI：
10.15424/bioelectronmed.2016.00001
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发表时间：
2016-01-01
影响因子：
--
通讯作者：
Tracey, Kevin J
中科院分区：
文献类型：
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作者：
Hanes, William M;Olofsson, Peder S;Tracey, Kevin J
当病原体和毒素突破上皮屏障时，抗原通过淋巴系统运送到淋巴结。在先前免疫过的动物中，抗原被困在引流淋巴结中，但控制抗原限制的潜在机制尚不清楚。在这里，我们描述了神经元在感知和限制抗原在淋巴结流动中的作用。抗原锁眼帽皮血青素（KLH）注射到小鼠后爪，从腘窝淋巴结流入坐骨淋巴结，继续通过上淋巴管进入体循环。与未接种的小鼠相比，先前免疫的小鼠再次暴露于KLH会导致从腘窝到坐骨淋巴结的流量减少。给予布比卡因进入淋巴结区域恢复免疫动物的抗原流动。相反，与假对照相比，使用磁刺激的神经激活显著减少了幼稚动物的抗原贩运。消融NaV1.8 +感觉神经元可显著降低免疫小鼠的抗原限制。FcgammaRI/FcepsilonRI的基因缺失也逆转了抗原限制。表达pgp9.5的神经元、FcgammaRI受体和标记抗原的共定位发生在抗原激发位点。总之，这些研究揭示了神经元回路通过需要NaV1.8和FcgammaR的途径调节抗原运输。
When pathogens and toxins breech the epithelial barrier, antigens are transported by the lymphatic system to lymph nodes. In previously immunized animals, antigens become trapped in the draining lymph nodes, but the underlying mechanism that controls antigen restriction is poorly understood. Here we describe the role of neurons in sensing and restricting antigen flow in lymph nodes. The antigen keyhole-limpet hemocyanin (KLH) injected into the mouse hind paw flows from the popliteal lymph node to the sciatic lymph node, continuing through the upper lymphatics to reach the systemic circulation. Re-exposure to KLH in previously immunized mice leads to decreased flow from the popliteal to the sciatic lymph node as compared with naive mice. Administering bupivacaine into the lymph node region restores antigen flow in immunized animals. In contrast, neural activation using magnetic stimulation significantly decreases antigen trafficking in naive animals as compared with sham controls. Ablating NaV1.8 + sensory neurons significantly reduces antigen restriction in immunized mice. Genetic deletion of FcgammaRI/FcepsilonRI also reverses the antigen restriction. Colocalization of PGP9.5-expressing neurons, FcgammaRI receptors and labeled antigen occurs at the antigen challenge site. Together, these studies reveal that neuronal circuits modulate antigen trafficking through a pathway that requires NaV1.8 and FcgammaR.