Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1.
Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1.
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DOI：
10.1084/jem.20030437
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发表时间：
2004-02-16
期刊：
影响因子：
--
通讯作者：
Blumberg RS
中科院分区：
文献类型：
--
作者：
Iijima H;Neurath MF;Nagaishi T;Glickman JN;Nieuwenhuis EE;Nakajima A;Chen D;Fuss IJ;Utku N;Lewicki DN;Becker C;Gallagher TM;Holmes KV;Blumberg RS
癌胚抗原相关细胞粘附分子1（CEACAM 1）是一种细胞表面分子，已被提出负调节T细胞功能。我们已经表明，CEACAM 1与特异性调节T辅助细胞（Th）1途径，T-bet介导的Th 1细胞因子信号，和Th 1介导的免疫病理学在体内。在效应期用抗小鼠CEACAM 1特异性单克隆抗体（mAb）CC 1处理的小鼠表现出与干扰素（IFN）-γ产生减少相关的三硝基苯磺酸结肠炎严重程度降低。尽管恶唑酮结肠炎已被报道为Th 2介导的，但用CCl mAb或CEACAM 1-Fc嵌合蛋白处理的小鼠显示结肠炎严重程度降低，与IFN-γ和T-bet活化的显著降低相关，而抗原4活化的信号转导子和活化子不受影响。白细胞介素-4和IFN-γ基因缺陷小鼠均表现出较轻的恶唑酮结肠炎诱导。直接连接的T细胞在体外与小鼠肝炎病毒刺突蛋白，天然配体的N-结构域的CEACAM 1，抑制幼稚细胞分化为Th 1，但不是Th 2细胞和激活Th 1，但不是Th 2细胞因子的产生。这些结果表明，CEACAM 1亚型是一类新的活化诱导的T细胞上的细胞表面分子，其在Th 1介导的炎症的特异性调节中起作用，例如与炎症性肠病相关的炎症。
Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell surface molecule that has been proposed to negatively regulate T cell function. We have shown that CEACAM1 is associated with specific regulation of T helper cell (Th)1 pathways, T-bet–mediated Th1 cytokine signaling, and Th1-mediated immunopathology in vivo. Mice treated with anti–mouse CEACAM1-specific monoclonal antibody (mAb) CC1 during the effector phase exhibited a reduced severity of trinitrobenzene sulfonic acid colitis in association with decreased interferon (IFN)-γ production. Although oxazolone colitis has been reported as Th2 mediated, mice treated with the CC1 mAb or a CEACAM1-Fc chimeric protein exhibited a reduced severity of colitis in association with a significant reduction of IFN-γ and T-bet activation, whereas signal transducer and activator of antigen 4 activation was unaffected. Both interleukin-4 and IFN-γ gene–deficient mice exhibited less severe colitis induction by oxazolone. Direct ligation of T cells in vitro with the murine hepatitis virus spike protein, a natural ligand for the N-domain of CEACAM1, inhibited the differentiation of naive cells into Th1 but not Th2 cells and activation of Th1 but not Th2 cytokine production. These results indicate that CEACAM1 isoforms are a novel class of activation-induced cell surface molecules on T cells that function in the specific regulation of Th1-mediated inflammation such as that associated with inflammatory bowel disease.
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