CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus
CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus
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DOI：
10.1182/blood-2009-08-237784
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发表时间：
2010-03-11
期刊：
影响因子：
20.3
通讯作者：
Bhandoola, Avinash
中科院分区：
文献类型：
--
作者：
Zlotoff, Daniel A.;Sambandam, Arivazhagan;Bhandoola, Avinash
T淋巴生成需要胸腺在整个成人生活中由骨髓来源的前体沉淀。祖细胞进入胸腺是有选择性的，但这种选择性的分子基础尚不完全清楚。趋化因子受体CCR9已被证明在这一过程中起重要作用。然而，缺乏CCR9的祖细胞仍然可以进入胸腺，这表明额外分子的作用。在这里，我们报告了趋化因子受体CCR7也是有效胸腺沉降所必需的。CCR7选择性地表达在骨髓祖细胞上，这些祖细胞先前被证明具有稳定胸腺的能力，而CCR7（-/-）祖细胞在稳定胸腺方面存在缺陷。我们进一步证明，在没有CCR9的情况下，CCR7维持胸腺稳定。缺乏CCR7和CCR9的小鼠早期胸腺祖细胞数量严重减少，在竞争性实验中，CCR7(-/-) CCR9（-/-）双敲除祖细胞几乎完全限制胸腺沉淀。然而，这些小鼠具有接近正常的胸腺细胞。胸腺内种群的代偿性扩张至少可以解释这种恢复的一部分。总之，我们的研究结果说明了趋化因子受体信号在胸腺沉降中的关键作用，并有助于澄清生理性胸腺沉降祖细胞的细胞身份。（《Blood》，2010;115:1897-1905）
T lymphopoiesis requires settling of the thymus by bone marrow-derived precursors throughout adult life. Progenitor entry into the thymus is selective, but the molecular basis of this selectivity is incompletely understood. The chemokine receptor CCR9 has been demonstrated to be important in this process. However, progenitors lacking CCR9 can still enter the thymus, suggesting a role for additional molecules. Here we report that the chemokine receptor CCR7 is also required for efficient thymic settling. CCR7 is selectively expressed on bone marrow progenitors previously shown to have the capacity to settle the thymus, and CCR7(-/-) progenitors are defective in settling the thymus. We further demonstrate that CCR7 sustains thymic settling in the absence of CCR9. Mice deficient for both CCR7 and CCR9 have severe reductions in the number of early thymic progenitors, and in competitive assays CCR7(-/-) CCR9(-/-) double knockout progenitors are almost completely restricted from thymic settling. However, these mice possess near-normal thymic cellularity. Compensatory expansion of intrathymic populations can account for at least a part of this recovery. Together our results illustrate the critical role of chemokine receptor signaling in thymic settling and help to clarify the cellular identity of the physiologic thymic settling progenitors. (Blood. 2010; 115: 1897-1905)