Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration.
Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration.
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DOI：
10.1038/ncomms5710
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发表时间：
2014-08-19
影响因子：
16.6
通讯作者：
Shibuya, Akira
中科院分区：
文献类型：
--
作者：
Totsuka, Naoya;Kim, Yun-Gi;Kanemaru, Kazumasa;Niizuma, Kouta;Umemoto, Eiji;Nagai, Kei;Tahara-Hanaoka, Satoko;Nakahasi-Oda, Chigusa;Honda, Shin-ichiro;Miyasaka, Masayuki;Shibuya, Kazuko;Shibuya, Akira
炎性单核细胞在宿主抵抗感染中发挥着重要作用。然而，转生到受感染组织的调节机制还没有完全了解。在这里，我们发现缺乏Mair-II(也称为CLM-4或LMIR2)的小鼠比野生型(WT)小鼠更容易患盲肠结扎和穿孔(CLP)引起的腹膜炎。过继转移来自WT小鼠的炎性单核细胞，而不是来自Mair-II、TLR4或MyD88缺陷小鼠的过继转移，显著提高了CLP后Mair-II缺陷小鼠的存活率。在上述突变和FcRγ链缺陷小鼠中，依赖于vla-4的炎性单核细胞在CLP后向腹膜腔内的迁移受到损害。脂多糖刺激可诱导Mair-II与FCRVCA1链和Syk结合，从而增强γ-4介导的对VCAM1的黏附。这些结果表明，TLR4/MYD88介导的MAIR-II/FCRVLA链的激活对于炎症单核细胞从血液到γ-4介导的感染部位的迁移至关重要。炎性单核细胞在宿主抵抗感染中发挥着重要作用。在这里，作者通过证明Toll样受体4和Mair-II免疫受体参与这一过程，提供了对炎性单核细胞向感染部位募集背后的机制的见解。
Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient in MAIR-II (also called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP)-induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice, significantly improves survival of MAIR-II-deficient mice after CLP. Migration of inflammatory monocytes into the peritoneal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcRγ chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcRγ chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcRγ chain by TLR4/MyD88-mediated signalling is essential for the transmigration of inflammatory monocytes from the blood to sites of infection mediated by VLA-4. Inflammatory monocytes play an important role in host defense against infections. Here the authors provide insights into the mechanism behind the recruitment of inflammatory monocytes to sites of infection by demonstrating the involvement of Toll-like receptor 4 and MAIR-II immunoreceptors in this process.
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影响因子：
4.8
作者：
Medvedev, Andrei E.;Piao, Wenji;Vogel, Stefanie N.
通讯作者：
Vogel, Stefanie N.
影响因子：
4.4
作者：
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11.2
作者：
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通讯作者：
Van Ginderachter, Jo A.
影响因子：
4.4
作者：
Nakahashi, Chigusa;Tahara-Hanaoka, Satoko;Shibuya, Akira
通讯作者：
Shibuya, Akira
影响因子：
32.4
作者：
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Núñez G