Langerhans cell histiocytosis (LCH) is characterized by an expansion and accumulation of pathological histiocytes expressing langerin (CD207) and CD1a in different organs under an inflammatory milieu. The origin of pathognomonic precursors of LCH is widely debated, but monocytes and pre-dendritic cells (pre-DC) play a significant role. Remarkably, we found an expansion of AXL cells in the CD11c subset of patients with active LCH, which also express the pathognomonic CD207 and CD1a. Moreover, we obtained a monocyte-derived LC-like (mo-LC-like) expressing high levels of AXL when treated with inflammatory cytokine, or plasma of patients with active disease. Intriguingly, inhibiting the mTOR pathway at the initial stages of monocyte differentiation to LC-like fosters the pathognomonic LCH program, highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXL could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.

中文翻译：

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AXLhigh 骨髓细胞增多，作为 Langerhans 细胞组织细胞增多症的病理标志物，以及 mTOR 抑制的 Langerin 表达依赖性

朗格汉斯细胞组织细胞增多症 (LCH) 的特征是炎症环境下不同器官中表达朗格汉斯蛋白 (CD207) 和 CD1a 的病理组织细胞的扩张和积累。 LCH 特异性前体细胞的起源存在广泛争议，但单核细胞和前树突细胞 (pre-DC) 发挥着重要作用。值得注意的是，我们发现活动性 LCH 患者的 CD11c 子集中 AXL 细胞扩增，这些细胞也表达特征性 CD207 和 CD1a。此外，当用炎症细胞因子或活动性疾病患者的血浆治疗时，我们获得了表达高水平 AXL 的单核细胞衍生的 LC 样（mo-LC 样）。有趣的是，在单核细胞向 LC 样分化的初始阶段抑制 mTOR 通路会促进特异的 LCH 程序，显着增加 CD207 水平以及 NOTCH1 诱导。我们在此定义AXL也可以作为LCH的强诊断标志物，Langerin和NOTCH1表达的释放取决于mTOR通路的抑制。