美国匹兹堡大学医学院Anthony J. St. Leger团队在研究中取得进展。他们揭示CD4 + T和髓样细胞产生细胞因子VEGF-A，破坏角膜神经图谱并促进疱疹基质性角膜炎（HSK）。相关论文于2020年11月17日发表在《免疫》杂志上。

他们使用1型单纯疱疹病毒（HSV-1）角膜感染的小鼠模型检查了VEGF-A对HSK潜在神经系统变化的影响。CD4 + T细胞和髓样细胞均在HSV-1感染的角膜内产生致病水平的VEGF-A，而CD4 +细胞耗竭则促进HSK角膜通过感觉神经的神经支配。在体外，来自感染角膜的VEGF-A抑制感觉神经生长并促进交感神经生长。

使用贝伐单抗在体内中和VEGF-A可抑制交感神经支配，促进感觉神经再生并减轻疾病。因此，VEGF-A可以塑造角膜内的感觉神经和交感神经，从而影响角膜致盲性疾病的治疗。

据了解，感染了HSV-1的角膜可发展为一种致盲的免疫炎性疾病，称为HSK，由于感觉神经的收缩和随后交感神经的过度神经支配，导致角膜敏感性丧失。角膜中细胞因子VEGF-A浓度升高与HSK严重程度有关。

附：英文原文

Title: Production of the Cytokine VEGF-A by CD4+ T and Myeloid Cells Disrupts the Corneal Nerve Landscape and Promotes Herpes Stromal Keratitis

Author: Hongmin Yun, Michael B. Yee, Kira L. Lathrop, Paul R. Kinchington, Robert L. Hendricks, Anthony J. St. Leger

Issue&Volume: 2020/11/17

Abstract: Herpes simplex virus type 1 (HSV-1)-infected corneas can develop a blinding immunoinflammatorycondition called herpes stromal keratitis (HSK), which involves the loss of cornealsensitivity due to retraction of sensory nerves and subsequent hyperinnervation withsympathetic nerves. Increased concentrations of the cytokine VEGF-A in the corneaare associated with HSK severity. Here, we examined the impact of VEGF-A on neurologicchanges that underly HSK using a mouse model of HSV-1 corneal infection. Both CD4+ T cells and myeloid cells produced pathogenic levels of VEGF-A within HSV-1-infectedcorneas, and CD4+ cell depletion promoted reinnervation of HSK corneas with sensory nerves. In vitro, VEGF-A from infected corneas repressed sensory nerve growth and promoted sympatheticnerve growth. Neutralizing VEGF-A in vivo using bevacizumab inhibited sympathetic innervation, promoted sensory nerve regeneration,and alleviated disease. Thus, VEGF-A can shape the sensory and sympathetic nerve landscapewithin the cornea, with implications for the treatment of blinding corneal disease.

DOI: 10.1016/j.immuni.2020.10.013

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30454-4