Chen Xinrong, Esplin Brandt L, Garrett Karla P, Welner Robert S, Webb Carol F, Kincade Paul W
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
J Immunol. 2008 Jan 1;180(1):138-45. doi: 10.4049/jimmunol.180.1.138.
Retinoids are known to have potent effects on hemopoietic stem cell integrity, and our objective was to learn whether they influence cells destined to replenish the immune system. Total CD19+ B lineage cells increased substantially in the marrow and spleens of all-trans retinoic acid (ATRA)-treated C57BL6 mice, while lymphoid progenitors were reduced. All B lymphoid progenitors were targets of ATRA in culture and overall cell yields declined without reductions in proliferation. Remarkably, ATRA shortened the time required for primitive progenitors to generate CD19+ cells. PCR analysis and a panel of retinoid acid receptor (RAR)/retinoid X receptor agonist treatments suggested that RARalpha mediates these responses. The transcription factors EBF1 and Pax-5 were elevated during treatment and ATRA had similar effects on human B cell differentiation. That is, it inhibited the expansion of human progenitor cells and accelerated their differentiation to B lineage cells. There may be previously unsuspected side effects of ATRA therapy, and the new findings suggest retinoids can normally contribute to the lymphopoietic environment in bone marrow.
已知视黄酸对造血干细胞完整性有显著影响，我们的目的是了解它们是否会影响注定要补充免疫系统的细胞。在全反式维甲酸（ATRA）处理的C57BL6小鼠的骨髓和脾脏中，总的CD19+B谱系细胞显著增加，而淋巴祖细胞减少。在培养中，所有B淋巴祖细胞都是ATRA的作用靶点，并且总体细胞产量下降，但增殖没有减少。值得注意的是，ATRA缩短了原始祖细胞产生CD19+细胞所需的时间。PCR分析和一组视黄酸受体（RAR）/视黄酸X受体激动剂处理表明，RARα介导了这些反应。在治疗过程中，转录因子EBF1和Pax-5升高，并且ATRA对人类B细胞分化有类似影响。也就是说，它抑制了人类祖细胞的扩增并加速了它们向B谱系细胞的分化。ATRA疗法可能存在以前未被怀疑的副作用，并且新发现表明视黄酸通常有助于骨髓中的淋巴细胞生成环境。
