Expression of a single ICAM-1 isoform on T cells is sufficient for development of experimental autoimmune encephalomyelitis.
Expression of a single ICAM-1 isoform on T cells is sufficient for development of experimental autoimmune encephalomyelitis.
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DOI：
10.1002/eji.201344023
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发表时间：
2014-04
影响因子：
5.4
通讯作者：
Barnum, Scott R.
中科院分区：
文献类型：
--
作者：
Bullard, Daniel C.;Hu, Xianzhen;Crawford, David;McDonald, Kristin;Ramos, Theresa N.;Barnum, Scott R.
关键词：
细胞间粘附分子-1（ICAM-1）在白细胞运输、诱导细胞免疫应答和免疫突触形成中起重要作用。作为粘附蛋白免疫球蛋白超家族的成员，ICAM-1由重复的Ig样结构域、跨膜结构域和参与细胞内信号传导事件的短胞质尾区组成。选择性剪接产生至少7种ICAM-1蛋白亚型，但对其免疫生物学知之甚少。我们先前已经使用不同系的ICAM-1突变小鼠（Icam 1 tm 1 Jcgr和Icam 1 tm 1Bay）表明，选择性剪接的ICAM-1亚型的表达可以显着影响EAE发展过程中的疾病过程。在这项研究中，我们使用一个新开发的转基因小鼠（CD 2-Icam 1 D4 del/Icam 1 null），T细胞特异性表达的一个单一的ICAM-1亚型组成的IG域1，2，3和5，可以介导的EAE的开始和进展。我们的研究结果表明，ICAM-1亚型缺乏IG域4可以驱动脱髓鞘疾病的发病机制，并可能成为治疗多发性硬化症的一个新的治疗靶点。
Intercellular adhesion molecule-1 (ICAM-1) plays an important role in leukocyte trafficking, induction of cellular immune responses, and immunological synapse formation. As a member of the immunoglobulin superfamily of adhesion proteins, ICAM-1 is composed of repeating Ig-like domains, a transmembrane domain, and short cytoplasmic tail that participates in intracellular signaling events. At least seven ICAM-1 protein isoforms are generated by alternative splicing, however little is known regarding their immunobiology. We have previously shown using different lines of ICAM-1 mutant mice (Icam1tm1Jcgr and Icam1tm1Bay) that expression of alternatively spliced ICAM-1 isoforms can significantly influence the disease course during the development of EAE. In this study, we show using a newly developed transgenic mouse (CD2-Icam1D4del/Icam1null) that T cell-specific expression of a single ICAM-1 isoform composed of Ig domains 1, 2, 3 and 5, can mediate the initiation and progression of EAE. Our results indicate that the ICAM-1 isoform lacking Ig domain 4 can drive pathogenesis in demyelinating disease and may be a novel therapeutic target for treating multiple sclerosis.
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影响因子：
5.4
作者：
Wohler, Jillian E.;Smith, Sherry S.;Zinn, Kurt R.;Bullard, Dan C.;Barnum, Scott R.
通讯作者：
Barnum, Scott R.
影响因子：
3.6
作者：
Hu X;Barnum SR;Wohler JE;Schoeb TR;Bullard DC
通讯作者：
Bullard DC
影响因子：
--
作者：
Giorelli, M;De Blasi, A;Trojano, M
通讯作者：
Trojano, M
影响因子：
5.1
作者：
Ochietti, B;Lemieux, P;Alakhov, V
通讯作者：
Alakhov, V
影响因子：
4.4
作者：
Szalai, AJ;Nataf, S;Barnum, SR
通讯作者：
Barnum, SR