The Chemokine Receptor CXCR4 Mediates Recruitment of CD11c+ Conventional Dendritic Cells Into the Inflamed Murine Cornea.
The Chemokine Receptor CXCR4 Mediates Recruitment of CD11c+ Conventional Dendritic Cells Into the Inflamed Murine Cornea.
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DOI：
10.1167/iovs.18-25084
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发表时间：
2018-11-01
影响因子：
4.4
通讯作者：
Hamrah P
中科院分区：
文献类型：
--
作者：
Lopez MJ;Seyed-Razavi Y;Jamali A;Harris DL;Hamrah P
角膜含有不同的抗原呈递细胞（APC）群体，包括常规树突状细胞（cDC）。关于cDC归巢和募集到幼稚和炎症角膜中的分子机制知之甚少。本研究的目的是研究CXCR 4及其配体CXCL 12在小鼠角膜中的存在及其在角膜炎症期间cDC迁移中的作用。CXCR 4和CXCL 12在未处理和缝线发炎的小鼠角膜中的表达通过整体包埋染色、流式细胞术和定量PCR进行评估。使用用针对CXCR 4的中和抗体阻断的cDC的过继转移来研究CXCR 4在募集到发炎角膜中的作用。我们发现趋化因子受体CXCR 4在总角膜CD 11 c + cDC中的表达率分别为51.7%和64.8%，相当于外周角膜中的98.6 ± 12.5个细胞/mm 2和中央幼稚角膜中的64.7 ± 10.6个细胞/mm 2。沿着炎症过程中CXCL 12表达增加4.5倍（P < 0.05），浸润的cDCs在外周和外周血中也表达CXCR 4，（222.6 ± 33.3）个/mm ~ 2，P < 0.001（161.9 ± 23.8个细胞/mm 2; P = 0.001），分别表示角膜中减少至31.0%和37.3%。此外，与用同种型对照预处理的细胞相比，用抗CXCR 4中和抗体的离体阻断（390.1 ± 40.1对612.1 ± 78.3; P = 0.008）和局部阻断（263.5 ± 27.1对807.5 ± 179.5，P < 0.001）导致cDC归巢到角膜中的减少。我们的结果表明，角膜CXCL 12在CXCR 4 + cDC募集到角膜中起直接作用。因此，CXCR 4/CXCL 12轴是调节角膜炎症反应的潜在靶点。
The cornea contains distinct populations of antigen-presenting cells (APCs), including conventional dendritic cells (cDCs). Little is known about the molecular mechanisms involved in cDCs homing and recruitment into the naïve and inflamed cornea. The purpose of this study was to investigate the presence of CXCR4 and its ligand CXCL12 in the murine cornea and its role in cDC migration during corneal inflammation. The expression of CXCR4 and CXCL12 in naïve and suture-inflamed murine corneas was assessed by whole-mount staining, flow cytometry, and quantitative PCR. The role of CXCR4 in recruitment into inflamed corneas was investigated using adoptive transfer of cDCs blocked with neutralizing antibody against CXCR4. We show the chemokine receptor CXCR4 to be expressed on 51.7% and 64.8% of total corneal CD11c+ cDCs, equating to 98.6 ± 12.5 cells/mm2 in the peripheral and 64.7 ± 10.6 cells/mm2 in the central naïve cornea, respectively. Along with a 4.5-fold increase in CXCL12 expression during inflammation (P < 0.05), infiltrating cDCs also expressed CXCR4 in both the peripheral (222.6 ± 33.3 cells/mm2; P < 0.001) and central cornea (161.9 ± 23.8 cells/mm2; P = 0.001), representing a decrease to 31.0% and 37.3% in the cornea, respectively. Further, ex vivo blockade (390.1 ± 40.1 vs. 612.1 ± 78.3; P = 0.008) and local blockade (263.5 ± 27.1 vs. 807.5 ± 179.5, P < 0.001) with anti-CXCR4 neutralizing antibody resulted in a decrease in cDCs homing into the cornea compared with cells pretreated with isotype controls. Our results demonstrate that corneal CXCL12 plays a direct role in CXCR4+ cDC recruitment into the cornea. The CXCR4/CXCL12 axis is therefore a potential target to modulate corneal inflammatory responses.
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影响因子：
4.8
作者：
Cook WJ;Kramer MF;Walker RM;Burwell TJ;Holman HA;Coen DM;Knipe DM
通讯作者：
Knipe DM
影响因子：
56.9
作者：
Campbell, JJ;Hedrick, J;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
56.9
作者：
Feng, Y;Broder, CC;Berger, EA
通讯作者：
Berger, EA
影响因子：
11.4
作者：
Dar, A.;Schajnovitz, A.;Lapid, K.;Kalinkovich, A.;Itkin, T.;Ludin, A.;Kao, W-M;Battista, M.;Tesio, M.;Kollet, O.;Cohen, N. N.;Margalit, R.;Buss, E. C.;Baleux, F.;Oishi, S.;Fujii, N.;Larochelle, A.;Dunbar, C. E.;Broxmeyer, H. E.;Frenette, P. S.;Lapidot, T.
通讯作者：
Lapidot, T.
DOI：
10.1073/pnas.94.5.1925
发表时间：
1997-03-04
影响因子：
11.1
作者：
Bleul, CC;Wu, LJ;Mackay, CR
通讯作者：
Mackay, CR