Loss of Neurokinin-1 Receptor Alters Ocular Surface Homeostasis and Promotes an Early Development of Herpes Stromal Keratitis.
Loss of Neurokinin-1 Receptor Alters Ocular Surface Homeostasis and Promotes an Early Development of Herpes Stromal Keratitis.
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DOI：
10.4049/jimmunol.1600836
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发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Suvas S
中科院分区：
文献类型：
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作者：
Gaddipati S;Rao P;Jerome AD;Burugula BB;Gerard NP;Suvas S
P物质神经肽及其受体神经激肽-1（NK 1 R）被报道存在于眼表。在这项研究中，缺乏功能性NK 1 R的小鼠表现出与上皮细胞增殖增加，上皮细胞密度增加，但上皮细胞大小减少相关的顶端角膜上皮细胞过度脱皮。NK 1 R的缺乏还导致角膜神经、角膜上皮树突状细胞的密度降低，以及基底泪液的体积减少。有趣的是，在NK 1 R −/−小鼠的球结膜和角膜缘区域附近观察到大量CD 11 c + CD 11b+常规树突状细胞（cDC）积聚。眼部HSV-1感染后，NK 1 R −/−小鼠中浸润感染角膜的cDC和中性粒细胞数量显著高于C57 BL/6 J小鼠。这与NK 1 R −/−小鼠感染角膜中的病毒载量增加有关。结果，NK 1 R −/−小鼠DLN中分泌IFN-γ的病毒特异性CD 4 T细胞的数量远高于感染的C57 BL/6 J小鼠。在NK 1 R −/−小鼠发炎的角膜中，CD 4 T细胞和成熟中性粒细胞（CD 11b + Ly 6 ghigh）数量的增加与严重HSK的早期发展有关。总的来说，我们的研究结果表明，未感染的NK 1 R −/−小鼠的角膜生物学改变沿着眼部HSV-1感染后增强的免疫反应导致NK 1 R −/−小鼠HSK的早期发展。
Substance P neuropeptide and its receptor neurokinin-1 (NK1R) are reported to present on the ocular surface. In this study, mice lacking functional NK1R exhibited an excessive desquamation of apical corneal epithelial cells in association with an increased epithelial cell proliferation, increased epithelial cell density, but decreased epithelial cell size. The lack of NK1R also resulted in decreased density of corneal nerves, corneal epithelial dendritic cells, and a reduced volume of basal tears. Interestingly, massive accumulation of CD11c+CD11b+ conventional dendritic cells (cDCs) was noted in the bulbar conjunctiva and near the limbal area of corneas from NK1R−/− mice. After ocular HSV-1 infection, the number of cDCs and neutrophils infiltrating the infected corneas was significantly higher in NK1R−/− than C57BL/6J mice. This was associated with an increased viral load in infected corneas of NK1R−/− mice. As a result, the number of IFN-γ secreting virus specific CD4 T cells in the DLNs of NK1R−/− mice was much higher than infected C57BL/6J mice. An increased number of CD4 T cells and mature neutrophils (CD11b+Ly6ghigh) in the inflamed corneas of NK1R−/− mice was associated with an early development of severe HSK. Collectively, our results show that the altered corneal biology of uninfected NK1R−/− mice along with an enhanced immunological response after ocular HSV-1 infection cause an early development of HSK in NK1R−/− mice.