IL-17 and VEGF Are Necessary for Efficient Corneal Nerve Regeneration
IL-17 and VEGF Are Necessary for Efficient Corneal Nerve Regeneration
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IL-17 和 VEGF 对于有效的角膜神经再生是必需的。
DOI：
10.1016/j.ajpath.2010.12.001
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发表时间：
2011-03-01
影响因子：
6
通讯作者：
Smith, C. Wayne
中科院分区：
文献类型：
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作者：
Li, Zhijie;Burns, Alan R.;Smith, C. Wayne
采用去除分层上皮和基底下神经丛的角膜磨损模型，研究了急性炎症对小鼠角膜感觉神经再生的贡献。磨损诱导的IL-17(+) CCR6(+) γ δ T细胞、中性粒细胞和血小板在角膜中积累，随后在96小时内上皮完全恢复，感觉神经再生率接近19%。缺乏γ δ T细胞（TCR δ(-/-)）的小鼠或全身注射抗il -17的野生型小鼠，白细胞和血小板浸润减少> 50%，神经再生减少> 50%。用于防止中性粒细胞和血小板积累的策略（例如，用抗ly6g或抗gp1b α抗体治疗野生型小鼠以消耗中性粒细胞或血小板）也导致角膜神经密度减少50%。浸润的中性粒细胞和血小板对VEGF-A染色呈阳性，组织中VEGF-A水平的峰值与中性粒细胞和血小板的峰值一致，损伤前中性粒细胞的消耗使组织中VEGF-A水平降低了> 70%，抗VEGF-A抗体治疗的野生型小鼠角膜神经再生减少了> 80%。鉴于已知的VEGF-A对神经突生长的营养作用，本报告的结果表明，在角膜神经再生中，涉及IL-17、中性粒细胞、血小板和VEGF-A的γ δ T细胞依赖性炎症级联反应具有以前未被认识到的有益作用。（中华病理学杂志，2011,178:1106-1116;DOI: 10.1016/ j.j ajpath.2010.12.001）
The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) gamma delta T cells, neutrophils, and platelets in the cornea followed by full restoration of the epithelium and similar to 19% regeneration of sensory nerves within 96 hours. Mice deficient in gamma delta T cells (TCR delta(-/-)) or wild-type mice treated systemically with anti-IL-17 had > 50% reduction in leukocyte and platelet infiltration and > 50% reduction in nerve regeneration. Strategies used to prevent neutrophil and platelet accumulation (eg, wild-type mice treated with anti-Ly6G or anti-GP1b alpha antibody to deplete neutrophils or platelets) also resulted in > 50% reductions in corneal nerve density. Infiltrating neutrophils and platelets stained positively for VEGF-A, tissue levels of VEGF-A peaked coincidentally with peak tissue levels of neutrophils and platelets, depletion of neutrophils before injury reduced tissue VEGF-A levels by > 70%, and wild-type mice treated systemically with anti-VEGF-A antibody exhibited > 80% reduction in corneal nerve regeneration. Given the known trophic effects of VEGF-A for neurite growth, the results in this report demonstrate a previously unrecognized beneficial role for the gamma delta T cell-dependent inflammatory cascade involving IL-17, neutrophils, platelets, and VEGF-A in corneal nerve regeneration. (Am J Pathol 2011, 178:1106-1116; DOI: 10.1016/j.ajpath.2010.12.001)