Division of Hematology, Oncology, and Transplantation, Department of Medicine.
Stem Cell Institute.
Curr Opin Hematol. 2018 Jul;25(4):273-278. doi: 10.1097/MOH.0000000000000432.
We summarize current advances to define the role the aryl hydrocarbon receptor (AHR) plays in mammalian hematopoiesis. We emphasize approaches to modulate AHR throughout human hematopoietic development in vitro to support the production of clinically relevant blood products suitable for patient care.
Initial data demonstrate that both pharmacologic AHR inhibition and genetic deletion from human pluripotent stem cells provide useful strategies to enhance the yield of hematopoietic stem and progenitor cells. AHR hyperactivation following the induction of CD34 megakaryocyte-erythroid progenitors skews developed toward erythroid lineages, whereas AHR inhibition supports platelet production. At the level of lymphoid specification, AHR inhibition enhances the proliferation and differentiation of functional human natural killer cells, whereas hyperactivation leads to production of Group 3 innate lymphoid cells and provides a novel platform for studying human innate lymphoid cell development.
Modulation of AHR in human hematopoietic cells in vitro is a promising tool to mediate development of terminal hematopoietic cell populations with significant clinical implications to generate cells suitable for antitumor immunotherapy and bone marrow transplantation.
我们总结了目前在哺乳动物造血中芳烃受体（AHR）作用的研究进展。我们强调了在体外调节 AHR 的方法，以支持生产适合患者护理的临床相关血液产品。
最初的数据表明，药物抑制 AHR 和基因敲除都可以从人类多能干细胞中提供有用的策略来提高造血干细胞和祖细胞的产量。在诱导 CD34 巨核细胞-红细胞祖细胞后，AHR 的过度激活会使发育偏向红细胞谱系，而 AHR 抑制则支持血小板的产生。在淋巴细胞的特化水平上，AHR 抑制增强了功能性人自然杀伤细胞的增殖和分化，而过度激活则导致 3 组固有淋巴细胞的产生，并为研究人固有淋巴细胞的发育提供了一个新的平台。
体外调节人造血细胞中的 AHR 是一种很有前途的工具，可以调节终末造血细胞群体的发育，对产生用于抗肿瘤免疫治疗和骨髓移植的细胞具有重要的临床意义。
