TRPA1 and TPRV1 Ion Channels Are Required for Contact Lens-Induced Corneal Parainflammation and Can Modulate Levels of Resident Corneal Immune Cells.
TRPA1 and TPRV1 Ion Channels Are Required for Contact Lens-Induced Corneal Parainflammation and Can Modulate Levels of Resident Corneal Immune Cells.
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DOI：
10.1167/iovs.64.11.21
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发表时间：
2023-08-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
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作者：
接触透镜配戴可诱导角膜副炎症，涉及CD 11 c+细胞应答（24小时）、γδ T细胞应答（24小时和6天）和IL-17依赖性Ly 6 G+细胞应答（6天）。局部抗生素阻断了这些CD 11 c+反应。由于角膜对细菌的CD 11 c+反应需要瞬时受体电位（TRP）离子通道（TRPA 1/TRPV 1），我们确定这些通道是否介导晶状体诱导的角膜副炎症。将野生型小鼠配戴隐形眼镜24小时或6天，并与配戴TRPA 1（-/-）或TRPV 1（-/-）的透镜小鼠或树脂毒素（RTX）处理的小鼠进行比较。侧眼未配戴镜片。通过定量成像检查角膜的主要组织相容性复合物（MHC）II类+、CD 45+、γδ T或TNF-α+细胞反应（24小时）或Ly 6 G+反应（6天）。定量PCR（qPCR）测定细胞因子基因表达。在TRPV 1（−/−）小鼠中，24小时后镜片诱导的MHC II类+细胞增加被消除，但TRPA 1（−/−）小鼠没有。CD 45+细胞的增加不受影响。在TRPA 1（−/−）和TRPV 1（−/−）小鼠中，佩戴24小时后γδ T细胞的增加被消除，6天Ly 6 G+细胞反应也是如此。TRPA 1（−/−）和TRPV 1（−/−）小鼠的侧角膜在24小时时显示MHC II类+和γδ T细胞减少。RTX抑制晶状体诱导的副炎症表型（24小时和6天），阻断晶状体诱导的TNF-α和IL-18基因表达、TNF-α+细胞浸润（24小时），并减少基线MHC II类+细胞。TRPA 1和TRPV 1介导配戴24小时和6天后角膜接触镜诱导的角膜副炎症，并可调节常驻角膜免疫细胞的基线水平。
Contact lens wear can induce corneal parainflammation involving CD11c+ cell responses (24 hours), γδ T cell responses (24 hours and 6 days), and IL-17-dependent Ly6G+ cell responses (6 days). Topical antibiotics blocked these CD11c+ responses. Because corneal CD11c+ responses to bacteria require transient receptor potential (TRP) ion-channels (TRPA1/TRPV1), we determined if these channels mediate lens-induced corneal parainflammation. Wild-type mice were fitted with contact lenses for 24 hours or 6 days and compared to lens wearing TRPA1 (−/−) or TRPV1 (−/−) mice or resiniferatoxin (RTX)-treated mice. Contralateral eyes were not fitted with lenses. Corneas were examined for major histocompatibility complex (MHC) class II+, CD45+, γδ T, or TNF-α+ cell responses (24 hours) or Ly6G+ responses (6 days) by quantitative imaging. The quantitative PCR (qPCR) determined cytokine gene expression. Lens-induced increases in MHC class II+ cells after 24 hours were abrogated in TRPV1 (−/−) but not TRPA1 (−/−) mice. Increases in CD45+ cells were unaffected. Increases in γδ T cells after 24 hours of wear were abrogated in TRPA1 (−/−) and TRPV1 (−/−) mice, as were 6 day Ly6G+ cell responses. Contralateral corneas of TRPA1 (−/−) and TRPV1 (−/−) mice showed reduced MHC class II+ and γδ T cells at 24 hours. RTX inhibited lens-induced parainflammatory phenotypes (24 hours and 6 days), blocked lens-induced TNF-α and IL-18 gene expression, TNF-α+ cell infiltration (24 hours), and reduced baseline MHC class II+ cells. TRPA1 and TRPV1 mediate contact lens-induced corneal parainflammation after 24 hours and 6 days of wear and can modulate baseline levels of resident corneal immune cells.
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影响因子：
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通讯作者：
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