Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor γδ+ gut intraepithelial lymphocytes
Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor γδ+ gut intraepithelial lymphocytes
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DOI：
10.1182/blood.v98.9.2626
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发表时间：
2001-11-01
期刊：
影响因子：
20.3
通讯作者：
Malissen, B
中科院分区：
文献类型：
--
作者：
Wurbel, MA;Malissen, M;Malissen, B
CC趋化因子受体(CCR)9是CC趋化因子CCL25/胸腺表达的趋化因子(Teck)的受体，主要由胸腺细胞、小肠上皮内(IEL)和固有层淋巴细胞表达。为了研究CCR9的生物学作用，建立了CCR9基因缺失的小鼠品系。尽管在双阳性和单阳性胸腺细胞中发现了CCR9的高水平及其相应的配体在胸腺基质细胞上的表达，但CCR9缺失对胸腺内T细胞的发育没有重大影响。我们注意到，在CCR9(-/-)胸腺的胚胎个体发育过程中，双阳性细胞的出现只有一天的滞后。在趋化试验中，从CCR9(-/-)小鼠分离的胸腺细胞对Teck/CCL25没有反应。综上所述，这些结果表明，在胸腺细胞中，CCR9是唯一的Teck/CCL25的生理受体，对于T细胞的正常发育是必不可少的。骨髓前-原B细胞在Teck/CCL25的作用下迁移，但更成熟的B细胞不会。与这一观察结果一致的是，CCR9(-/-)小鼠的Pre-Pro-B细胞比野生型小鼠少。然而，这种减少似乎对成熟B细胞的正常补充的产生没有可检测到的影响。最后，研究表明，在CCR9缺陷小鼠的小肠中，上皮内T细胞与上皮细胞的比率降低，这可以归因于T细胞受体伽马增量(+)区的显著减少。(C)2001年，由美国血液病学会提供。
CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/thymus-expressed chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small Intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was deleted. In spite of the high level of CCR9 found in double-and single-positive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrathymic T-cell develop ment. It was noted that there was only a one-day lag In the appearance of double-positive cells during fetal ontogeny in CCR9(-/-) thymi. When tested in chemotaxis assay, thymocytes isolated from CCR9(-/-) mice failed to respond to TECK/CCL25. Taken together, these results suggest that In thymocytes, CCR9 is the only physiologic receptor for TECK/CCL25, and that it is dispensable for proper T-cell development. Bone marrow pre-pro-B cells migrate in response to TECK/CCL25, but more mature B cells do not. Consistent with this observation, it was shown that there are fewer pre-pro-B cells in CCR9(-/-) mice than in wild-type mice. However, this diminution does not appear to have a detectable effect on the generation of a normal complement of mature B cells. Finally, it was shown that in the small intestine of CCR9-deficient mice, the intraepithelial T-cell-to-epithelial cell ratio Is decreased, an observation that can be accounted for by a marked diminution of the T-cell receptor gamma delta (+) compartment. (C) 2001 by The American Society of Hematology.