Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina.
Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina.
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DOI：
10.1167/iovs.61.12.19
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发表时间：
2020-10-01
影响因子：
4.4
通讯作者：
Elliott MH
中科院分区：
文献类型：
--
作者：
Gurley JM;Gmyrek GB;McClellan ME;Hargis EA;Hauck SM;Dozmorov MG;Wren JD;Carr DJJ;Elliott MH
免疫特权环境和视网膜组织的复杂组织支持视网膜在视觉功能中的重要作用，但混淆了导致功能障碍和变性的细胞特异性炎症效应的调查。Caveolin-1 （Cav1）是一种完整的膜蛋白，在几种视网膜细胞类型中表达，并参与免疫调节。然而，Cav1是促进还是抑制视网膜（以及其他组织）的炎症过程仍不清楚。先前，我们发现全局cav1缺失导致视网膜炎症细胞因子产生减少，但矛盾的是视网膜免疫细胞浸润升高。我们假设这些不同的反应是视网膜中不同细胞特异性Cav1功能的结果。我们使用Cre/lox技术在神经视网膜（NR）隔室中特异性地消耗Cav1，以阐明NR特异性Cav1 （NR-Cav1）在由toll样受体-4 （TLR4）激活诱导的玻璃体内炎症攻击的视网膜免疫应答中的作用。我们使用多重蛋白悬浮阵列和流式细胞术来评估先天免疫激活。此外，我们使用生物信息学评估差异表达的膜相关蛋白来推断NR-Cav1与免疫反应途径之间的关系。NR-Cav1缺失，主要影响<s:2>神经胶质细胞Cav1的表达，显著改变免疫反应通路调节因子，减少视网膜炎症细胞因子的产生，减少视网膜免疫细胞浸润，以响应lps刺激的炎症诱导。NR室中Cav1的表达促进tlr4介导的先天性视网膜组织免疫反应。此外，我们已经确定了新的潜在的免疫调节剂在NR-Cav1缺失时差异表达。本研究进一步阐明了NR-Cav1在视网膜炎症中的作用。
The immune-privileged environment and complex organization of retinal tissue support the retina's essential role in visual function, yet confound inquiries into cell-specific inflammatory effects that lead to dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in several retinal cell types and is implicated in immune regulation. However, whether Cav1 promotes or inhibits inflammatory processes in the retina (as well as in other tissues) remains unclear. Previously, we showed that global-Cav1 depletion resulted in reduced retinal inflammatory cytokine production but paradoxically elevated retinal immune cell infiltration. We hypothesized that these disparate responses are the result of differential cell-specific Cav1 functions in the retina. We used Cre/lox technology to deplete Cav1 specifically in the neural retinal (NR) compartment to clarify the role NR-specific Cav1 (NR-Cav1) in the retinal immune response to intravitreal inflammatory challenge induced by activation of Toll-like receptor-4 (TLR4). We used multiplex protein suspension array and flow cytometry to evaluate innate immune activation. Additionally, we used bioinformatics assessment of differentially expressed membrane-associated proteins to infer relationships between NR-Cav1 and immune response pathways. NR-Cav1 depletion, which primarily affects Müller glia Cav1 expression, significantly altered immune response pathway regulators, decreased retinal inflammatory cytokine production, and reduced retinal immune cell infiltration in response to LPS-stimulated inflammatory induction. Cav1 expression in the NR compartment promotes the innate TLR4-mediated retinal tissue immune response. Additionally, we have identified novel potential immune modulators differentially expressed with NR-Cav1 depletion. This study further clarifies the role of NR-Cav1 in retinal inflammation.
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小窝蛋白-1蛋白在发育中的视网膜中的空间和时间定位。
影响因子：
--
作者：
Gu, Xiaowu;Reagan, Alaina;Yen, Allen;Bhatti, Faizah;Cohen, Alex W.;Elliott, Michael H.
通讯作者：
Elliott, Michael H.
LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
影响因子：
8.8
作者：
Fernandez-Rojo, Manuel A.;Gongora, Milena;Parton, Robert G.
通讯作者：
Parton, Robert G.
影响因子：
4.4
作者：
Garrean, Sean;Gao, Xiao-Pei;Malik, Asrar B.
通讯作者：
Malik, Asrar B.
影响因子：
3.8
作者：
Dillon, Christopher P.;Balachandran, Siddharth
通讯作者：
Balachandran, Siddharth