Homeostasis of Langerhans and Dendritic Cells in Health and Disease

树突状细胞是免疫系统的重要组成部分。它们检测异物并协调免疫反应。如果没有它们，对病毒、肿瘤和疫苗的免疫力就会严重受损。它们在移植器官的排斥反应和骨髓移植的并发症“移植物抗宿主病”中起着重要作用。此外，它们在组织细胞增多症中繁殖和积累，这是一种罕见但可能致命的疾病。我们正在研究的问题是这些细胞在体内是如何维持的。此前，人们认为它们会以稳定的速度被血液中的细胞取代。最近来自老鼠的证据表明，它们可以增殖或自我更新，但这在人类身上是未知的。我们认为1)人类皮肤树突状细胞是否能够自我更新；2)是什么控制了它们的存活和增殖；3)它们是否受到骨髓衰竭的影响。我们将使用从整形手术中获得的正常人类皮肤和来自特定骨髓疾病患者的小样本。我们的实验将有助于理解免疫系统在健康和疾病中是如何控制的，包括骨髓衰竭和移植。我们可能会发现加强疫苗接种、防止有害免疫反应和治疗组织细胞增多症的新方法。

Dendritic cells are critical components of the immune system. They detect foreign material and coordinate the immune response. Without them immunity to viruses, tumours and vaccines is severely compromised. They are important in the rejection of transplanted organs and in ‘graft versus host disease‘, a complication of bone marrow transplantation. Additionally, they multiply and accumulate in ‘histiocytosis‘, a rare but potentially fatal disease.The question we are studying is how these cells are maintained in the body. Previously they were thought to be replaced at a steady rate by cells from the blood. Recent evidence from mice suggests that they can proliferate or renew themselves but this is not known in humans. We propose to find out 1) whether human skin dendritic cells can renew themselves; 2) what controls their survival and proliferation; 3) whether they are affected by bone marrow failure. We will use normal human skin obtained from plastic surgery and small samples from patients with specific bone marrow disorders. Our experiments will help to understand how the immune system is controlled in health and disease, including bone marrow failure and transplantation. We may identify new ways to boost vaccination, prevent harmful immune responses and treat histiocytosis