Otto Loewi Research Center, Chair of Immunology and Pathophysiology, Medical University of Graz, Graz, Austria.
Otto Loewi Research Center, Chair of Immunology and Pathophysiology, Medical University of Graz, Graz, Austria.
Semin Cell Dev Biol. 2019 Feb;86:36-43. doi: 10.1016/j.semcdb.2018.02.016. Epub 2018 Feb 23.
Human Langerhans cells (LC) can be generated ex vivo from hematopoietic precursor cells in response to cytokines and cell-membrane associated ligands. These in vitro differentiation models provided mechanistic insights into the molecular and cellular pathways underlying the development of this unique, epithelia-associated dendritic cell subset. Notably, the human epidermal microenvironment is fully sufficient to induce LC differentiation from hematopoietic progenitors. Hence, dissecting the molecular characteristics of the human epithelial/epidermal LC niche, and testing defined ligands for their capacity to induce LC differentiation, led to a refined molecular model of LC lineage commitment. During epidermal ontogeny, spatially and temporally regulated availability of TGF-β family members cooperate with other keratinocyte-derived signals, such as E-cadherin and Notch ligands, for instructing LC differentiation. In this review, we discuss the signals known to instruct human hematopoietic progenitor cells and myelomonocytic cells to undergo LC lineage commitment. Additionally, the current methods for generation of large numbers of human LC-like cells ex vivo in defined serum-free media are discussed.
人类朗格汉斯细胞（LC）可在细胞因子和细胞膜相关配体的作用下，从造血前体细胞中体外生成。这些体外分化模型为理解LC 这一独特的上皮相关树突状细胞亚群发育的分子和细胞途径提供了机制上的见解。值得注意的是，人类表皮微环境完全足以诱导造血祖细胞向 LC 分化。因此，解析人上皮/表皮 LC 龛位的分子特征，并测试特定配体诱导 LC 分化的能力，导致 LC 谱系决定的分子模型得到了进一步完善。在表皮发生过程中，时空调节的 TGF-β 家族成员与其他角质形成细胞衍生的信号（如 E-钙黏蛋白和 Notch 配体）合作，指导 LC 分化。在这篇综述中，我们讨论了已知指导人类造血前体细胞和髓样细胞向 LC 谱系决定的信号。此外，还讨论了目前在无血清定义培养基中外源性大量生成类人 LC 细胞的方法。
