CTACK/CCL27 accelerates skin regeneration via accumulation of bone marrow-derived keratinocytes
CTACK/CCL27 accelerates skin regeneration via accumulation of bone marrow-derived keratinocytes
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DOI：
10.1634/stemcells.2006-0264
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发表时间：
2006-12-01
期刊：
影响因子：
5.2
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Inokuma, Daisuke;Abe, Riichiro;Shimizu, Hiroshi
最近的研究表明，骨髓（BM）细胞转分化以再生多种细胞谱系。由于每个器官中BM来源的细胞群体相对较小，这些BM来源的细胞是否真的以足够数量存在以实现有效功能仍然存在争议。相反，推测趋化因子/趋化因子受体相互作用介导组织特异性前体细胞从BM迁移到靶组织中。在这里，我们表明，皮肤T细胞吸引趋化因子（CTACK）/CCL 27是参与角质形成细胞前体细胞从BM迁移到皮肤的主要调节因子。通过筛选不同的趋化因子表达模式，我们证明CTACK在正常皮肤中组成性表达，在伤口中上调，大约20%的CD 34（+）BM细胞表达CTACK的配体CCR 10。将CTACK/CCL 27皮内注射到皮肤伤口的外周中显著增强BM衍生的角质形成细胞（BMDK）迁移，并且CTACK/CCL 27中和抗体抑制该BMDK迁移。此外，由CTACK/CCL 27引起的增加的BMDK迁移显著加速伤口愈合过程，而对血管生成或角质形成细胞增殖没有任何影响。这些结果提供了直接证据，即BM角质形成细胞前体细胞向皮肤的募集受特定趋化因子/趋化因子受体相互作用的调节，使得新的再生治疗策略的开发成为可能。
Recent studies have suggested that bone marrow ( BM) cells transdifferentiate to regenerate a variety of cellular lineages. Due to the relatively small population of BM- derived cells in each organ, it is still controversial whether these BM- derived cells are really present in sufficient numbers for effective function. Conversely, it is speculated that chemokine/ chemokine receptor interactions mediate this migration of the tissue- specific precursor cells from BM into the target tissue. Here, we show that cutaneous T- cell attracting chemokine ( CTACK)/ CCL27 is the major regulator involved in the migration of keratinocyte precursor cells from BM into skin. By screening various chemokine expression patterns, we demonstrated that CTACK is constitutively expressed in normal skin and upregulated in wounds and that approximately 20% of CD34(+) BM cells expressed CCR10, the ligand for CTACK. Intradermal injection of CTACK/ CCL27 into the periphery of skin wounds significantly enhanced BM- derived keratinocyte ( BMDK) migration, and CTACK/ CCL27 neutralizing antibody inhibited this BMDK migration. Furthermore, increased BMDK migration caused by CTACK/ CCL27 significantly accelerated the wound- healing process without any influence over either angiogenesis or keratinocyte proliferation. These results provide direct evidence that recruitment of BM keratinocyte precursor cells to the skin is regulated by specific chemokine/ chemokine receptor interactions, making possible the development of new regenerative therapeutic strategies.