Chemokines regulate lymphocyte homing to the intestinal mucosa.
Chemokines regulate lymphocyte homing to the intestinal mucosa.
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趋化因子调节淋巴细胞归巢至肠粘膜。
DOI：
10.1053/gast.2001.21403
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发表时间：
2001
期刊：
影响因子：
29.4
通讯作者：
A. Luster
中科院分区：
文献类型：
--
作者：
A. Luster
粘液T淋巴细胞在调节胃肠道免疫应答中起重要作用。这不是一项简单的任务，因为肠粘膜是宿主组织和环境之间的主要界面。区分正常细菌植物群和食物相关抗原与致病性细菌和毒素是至关重要的，并且在很大程度上受粘膜中的T细胞调节。在过去的几年中，已经清楚的是，失调的T细胞应答在胃肠道的炎性疾病中起致病作用。因此，了解控制肠道中淋巴细胞运输和活化的信号与宿主防御和炎症性肠病都有关。肠粘膜是不寻常的，因为它含有大量的T淋巴细胞，弥漫分布在整个固有层和上皮细胞。这些T细胞中的大多数是记忆细胞（CD 45 RO+），并表达指示最近激活的受体（即CD 25）。因此，人们认为上皮内淋巴细胞（IEL）和固有层淋巴细胞（LPL）是先前激活的/记忆细胞，在肠道相关淋巴组织（例如派伊尔氏结）中激活后被募集到肠粘膜中。调节这些细胞从这些专门的淋巴结构（在那里它们识别并被特异性抗原激活）选择性运输到粘膜中的分子机制还不完全清楚。在这一期的《胃学-动物学》中有两篇文章讨论了这个重要的主题。3，4白细胞从血液外渗到组织中是一个受调节的多步骤过程，涉及一系列协调的白细胞-内皮细胞相互作用。[5]几个分子调节因子家族，如选择素、整合素和趋化因子，被认为控制着这一过程的不同方面。在多步骤模型中，白细胞外渗开始于白细胞滚动，这是一个依赖于选择素的过程。滚动到牢固粘附的转换依赖于白细胞整合素的活化。越来越多的证据支持趋化因子作为白细胞整合素的重要活化剂的作用，从而提供决定何时何地以及哪个白细胞亚群将进入组织的关键信号。6淋巴细胞是一种迁移性细胞，最初从骨髓中的起源部位运输到胸腺，然后在血液和外周的特化淋巴和淋巴外组织之间持续再循环。7这些幼稚细胞被预先编程为具有这些次级淋巴器官（即派尔集合淋巴结和淋巴结）的向性。然而，抗原特异性活化似乎重新编程外周中幼稚T和B细胞的运输特性。记忆细胞和效应细胞比它们的幼稚前体更有效地归巢到组织炎症的淋巴结外部位，并显示出显著的选择性，用于运输到产生抗原刺激的胃肠道、皮肤或其他特定器官。这种抗原反应性群体的组织特异性靶向被认为通过循环记忆细胞增加免疫监视的效率，以及增强局部免疫应答。
Mucosal T lymphocytes play an important role in regulating gastrointestinal immune response. This is no trivial task because the intestinal mucosa is the main interface between host tissues and the environment. Discriminating normal bacterial flora and food-related antigens from pathogenic bacteria and toxins is critically important and in large part is regulated by T cells in the mucosa. It has become clear over the last several years that a dysregulated T-cell response plays a pathogenic role in inflammatory diseases of the gastrointestinal track. Therefore, understanding the signals that control lymphocyte trafficking and activation in the gut is relevant to both host defense and inflammatory bowel disease. The intestinal mucosa is unusual in that it contains large populations of T lymphocytes that are distributed diffusely throughout the lamina propria and epithelium. 1, 2 The majority of these T cells are memory cells (CD45RO+) and express receptors (ie, CD25) that indicate recent activation. Thus, intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) are believed to be previously activated/memory cells recruited into the intestinal mucosa after activation in gut-associated lymphoid tissue, such as Peyer’s patches. The molecular mechanisms regulating the selective trafficking of these cells from these specialized lymphoid structures, where they recognize and become activated by specific antigens, into the mucosa are not completely understood. Two articles in this issue of GASTROENTER-OLOGY address this important subject. 3, 4 Leukocyte extravasation from the blood into the tissues is a regulated multistep process involving a series of coordinated leukocyte–endothelial cell interactions. 5 Several families of molecular regulators such as the selectins, the integrins, and the chemokines are thought to control different aspects of the process. In the multistep model, leukocyte extravasation begins with leukocyte rolling, a process that is dependent on selectins. Conversion of rolling to firm adherence depends on the activation of leukocyte integrins. Increasing evidence supports a role for chemokines as important activators of leukocyte integrins, thereby providing critical signals determining where, when, and which leukocyte subset will enter a tissue. 6Lymphocytes are migratory cells, which initially traffic from their site of origin in the bone marrow to the thymus, and then continuously recirculate between blood and specialized lymphoid and extralymphoid tissue in the periphery. 7 These naive cells are preprogrammed with a tropism for these secondary lymphoid organs (ie, Peyer’s patches and lymph nodes). However, antigen-specific activation seems to reprogram the trafficking properties of naive T and B cells in the periphery. Memory and effector cells home much more effectively than their naive precursors to extralymphoid sites of tissue inflammation and display striking selectivity for trafficking to the gastrointestinal tract, skin, or other specific organs where the antigenic stimulus arose. This tissue-specific targeting of antigen-reactive populations is thought to increase the efficiency of immune surveillance by circulating memory cells, as well as enhancing local immune responses.
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影响因子：
15.9
作者：
Mach, F;Sauty, A;Luster, AD
通讯作者：
Luster, AD
影响因子：
4.4
作者：
Alain Sauty;Michelle Dziejman;R. Taha;Albert S. Iarossi;K. Neote;Eduardo A. Garcia-Zepeda;Qutayba A. Hamid;Andrew D. Luster
通讯作者：
Alain Sauty;Michelle Dziejman;R. Taha;Albert S. Iarossi;K. Neote;Eduardo A. Garcia-Zepeda;Qutayba A. Hamid;Andrew D. Luster
影响因子：
29.4
作者：
Dwinell, MB;Lügering, N;Kagnoff, MF
通讯作者：
Kagnoff, MF
影响因子：
4.4
作者：
Carlo Agostini;M. Cassatella;R. Zambello;L. Trentin;S. Gasperini;Alessandra Perin;F. Piazza;M. Siviero;M. Facco;Michelle Dziejman;M. Chilosi;Shixin Qin;A. Luster;G. Semenzato
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Carlo Agostini;M. Cassatella;R. Zambello;L. Trentin;S. Gasperini;Alessandra Perin;F. Piazza;M. Siviero;M. Facco;Michelle Dziejman;M. Chilosi;Shixin Qin;A. Luster;G. Semenzato
影响因子：
4.4
作者：
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通讯作者：
Andrew C. Novick;Hiroshi Toma;Robert L. Fairchild;S. Koga;M. B. Auerbach;T. Engeman