Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity.

Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity.
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DOI:
10.1084/jem.192.5.761
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发表时间:
2000-09-04
影响因子:
15.3
通讯作者:
Agace, W W
Agace, W W
中科院分区:
医学1区
文献类型:
--
作者:
Kunkel, E J;Campbell, J J;Haraldsen, G;Pan, J;Boisvert, J;Roberts, A I;Ebert, E C;Vierra, M A;Goodman, S B;Genovese, M C;Wardlaw, A J;Greenberg, H B;Parker, C M;Butcher, E C;Andrew, D P;Agace, W W

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免疫系统已经进化出专门的细胞和分子机制,用于靶向和调节上皮表面的免疫应答。在这里,我们表明,小肠上皮内淋巴细胞和固有层淋巴细胞迁移到胸腺表达的趋化因子(TECK)。这种吸引由CC趋化因子受体(CCR)9介导,CC趋化因子受体9是小肠中基本上所有CD 4+和CD 8 + T淋巴细胞以高水平表达的化学引诱物受体。结肠中只有一小部分淋巴细胞是CCR 9+,其他组织中的淋巴细胞包括扁桃体、肺、发炎的肝脏、正常或发炎的皮肤、发炎的滑膜和滑液、母乳和精液都是CCR 9-。TECK表达也仅限于小肠:免疫组织化学显示,强烈的抗TECK反应性表征空肠和回肠中的隐窝上皮,但不包括消化道(包括胃和结肠)、皮肤、肺或唾液腺的其他上皮。这些结果意味着淋巴细胞CCR 9及其配体TECK在小肠中的作用有限,并提供了第一个证据淋巴细胞募集的独特机制,可能允许在胃肠道的不同部分的免疫反应的功能专业化。分化上皮细胞选择性表达趋化因子可能是免疫应答靶向和特化的重要机制。
The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4+ and CD8+ T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9+, and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9−. TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.