Differential ICAM-1 isoform expression regulates the development and progression of experimental autoimmune encephalomyelitis.
Differential ICAM-1 isoform expression regulates the development and progression of experimental autoimmune encephalomyelitis.
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DOI：
10.1016/j.molimm.2010.03.005
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发表时间：
2010-05
影响因子：
3.6
通讯作者：
Bullard DC
中科院分区：
文献类型：
--
作者：
Hu X;Barnum SR;Wohler JE;Schoeb TR;Bullard DC
细胞间粘附分子 1 (ICAM-1) 在白细胞运输、激活和免疫突触形成中发挥作用。 ICAM-1 是粘附蛋白免疫球蛋白超家族的成员，其具有相似的重复 Ig 样结构域结构。该家族中的许多基因，包括 ICAM-1，显示出选择性剪接，导致产生不同的蛋白质亚型，尽管关于这些亚型的表达模式、配体相互作用和功能的功能信息很少，尤其是那些由 ICAM-1 基因产生的亚型。在这项研究中，我们使用不同品系的突变小鼠（Icam1tm1Jcgr 和 Icam1tm1Bay）证明，选择性剪接的 ICAM-1 亚型表达的改变可以显着影响 EAE 发展过程中的病程。与 Icam1tm1Bay 突变体不同，Icam1tm1Jcgr 突变体小鼠不表达含有 Mac-1 结合域的亚型，并且 EAE 显着减弱。相比之下，与 Icam1tm1Jcgr 和野生型小鼠相比，Icam1tm1Bay 小鼠在主动和过继转移模型中均出现严重的 EAE。我们还观察到，与 Icam1tm1Jcgr 和野生型小鼠相比，来自 Icam1tm1Bay 小鼠的 T 细胞表现出更高的增殖动力学，并产生更高水平的 IFN-γ。因此，我们的研究表明，选择性剪接的 ICAM-1 亚型具有功能性，并且在 EAE 中 CNS 炎症和脱髓鞘的进展过程中发挥关键作用。此外，我们的研究结果表明，这些亚型也可能在控制多发性硬化症等炎症性疾病的发展中发挥关键作用，这可能是通过与 ICAM-1 配体（如 Mac-1）的差异性结合来实现的。
Intercellular adhesion molecule-1 (ICAM-1) functions in leukocyte trafficking, activation, and the formation of the immunological synapse. ICAM-1 is a member of the immunoglobulin superfamily of adhesion proteins, which share a similar structure of repeating Ig-like domains. Many genes in this family, including ICAM-1, show alternative splicing leading to the production of different protein isoforms, although little functional information is available regarding the expression patterns, ligand interactions, and functions of these isoforms, especially those arising from the ICAM-1 gene. In this study, we show using different lines of mutant mice (Icam1tm1Jcgr and Icam1tm1Bay) that alterations in the expression of the alternatively spliced ICAM-1 isoforms can significantly influence the disease course during the development of EAE. Icam1tm1Jcgr mutant mice, unlike Icam1tm1Bay mutants, do not express isoforms containing the Mac-1 binding domain and had significantly attenuated of EAE. In contrast, Icam1tm1Bay mice developed severe EAE in both active and adoptive transfer models compared to both Icam1tm1Jcgr and wild type mice. We also observed that T cells from Icam1tm1Bay mice displayed increased proliferation kinetics and produced higher levels of IFN-γ compared to Icam1tm1Jcgr and wild type mice. Thus, our investigations show that the alternatively spliced ICAM-1 isoforms are functional, and play key roles during the progression of CNS inflammation and demyelination in EAE. Furthermore, our findings suggest that these isoforms may also play key roles in controlling the development of inflammatory diseases such as multiple sclerosis, possibly through differential engagement with ICAM-1 ligands such as Mac-1.
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影响因子：
3.2
作者：
Leung, E;Berg, RW;Krissansen, GW
通讯作者：
Krissansen, GW
影响因子：
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Giorelli, M;De Blasi, A;Trojano, M
通讯作者：
Trojano, M
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通讯作者：
Alakhov, V
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通讯作者：
Liblau, Roland S.
影响因子：
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作者：
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通讯作者：
O'Connor, PW