Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Mexico City, Mexico; National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico.
Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Mexico City, Mexico; Leukemia Clinic, Federico Gómez Children's Hospital, Mexico City, Mexico.
Exp Hematol. 2014 Jul;42(7):562-73.e3. doi: 10.1016/j.exphem.2014.03.008. Epub 2014 Apr 8.
Remarkable progress has been made in characterizing factors controlling lineage fate decisions of primitive progenitors that initiate the lymphoid program in bone marrow. However, the understanding of neonatal/adult differences in environmental signals that influence differentiation pathway stability is still incomplete. Our recent findings suggest that Toll-like receptors provide a mechanism for producing cells of the innate immune system from early stages of lymphoid development in mice. We now show that both human early multilymphoid progenitors and more differentiated lymphoid progenitors from normal adult bone marrow express TLR9. Furthermore, they respond to its ligation by upregulating the expression of IL-15Rβ (CD122) and accelerating the production of functional natural killer (NK)-like cells. Proliferation of the presumed equivalent progenitor cells from umbilical cord blood was stimulated by CpG-containing oligonucleotides or herpes simplex virus, but the already robust NK-cell formation was unchanged. This new information adds to other known differences between neonatal and adult lymphoid progenitors and suggests only the latter replenish innate NK-like cells in response to Toll-like receptor agonists.
在描述控制骨髓中启动淋巴谱系命运决定的原始祖细胞的因素方面已经取得了显著进展。然而，对于影响分化途径稳定性的环境信号在新生儿/成人中的差异的理解仍不完整。我们最近的研究结果表明，Toll 样受体为从小鼠的淋巴样发育早期产生固有免疫系统细胞提供了一种机制。我们现在表明，人类早期多淋巴样祖细胞和来自正常成人骨髓的更分化的淋巴样祖细胞均表达 TLR9。此外，它们通过上调白细胞介素 15Rβ（CD122）的表达并加速功能性自然杀伤（NK）样细胞的产生来对其配体进行反应。CpG 含有寡核苷酸或单纯疱疹病毒刺激假定的等效祖细胞的增殖，但已经强大的 NK 细胞形成没有改变。这些新信息增加了新生儿和成人淋巴样祖细胞之间的其他已知差异，并表明只有后者在 Toll 样受体激动剂的作用下补充固有 NK 样细胞。
