Lack of Conventional Dendritic Cells Is Compatible with Normal Development and T Cell Homeostasis, but Causes Myeloid Proliferative Syndrome
Lack of Conventional Dendritic Cells Is Compatible with Normal Development and T Cell Homeostasis, but Causes Myeloid Proliferative Syndrome
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DOI：
10.1016/j.immuni.2008.10.012
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发表时间：
2008-12-19
期刊：
影响因子：
32.4
通讯作者：
Jung, Steffen
中科院分区：
文献类型：
--
作者：
Birnberg, Tal;Bar-On, Liat;Jung, Steffen
树突状细胞在T细胞反应的促进和调节中起重要作用。在这里，我们报告了一个缺乏传统CD11c(Hi)树突状细胞(CDCs)的小鼠品系，这是因为自杀基因的构成细胞型特异性表达。正如预期的那样，CDC缺失的小鼠未能产生有效的T细胞反应，导致病毒清除受损。相反，胸腺负选择和T调节细胞生成或T细胞稳态都没有受到明显影响。出乎意料的是，CDC缺乏的小鼠发展为进行性骨髓增殖性疾病，其特征是突出的髓外造血和血清中细胞因子Flt3配体的数量增加。我们的数据确定了CDCs在控制稳态造血中的关键作用，揭示了一个反馈回路，通过可溶性生长因子，如Flt3配体，将外周CDCs与骨髓生成联系起来。
Dendritic cells are critically involved in the promotion and regulation of T cell responses. Here, we report a mouse strain that lacks conventional CD11c(hi) dendritic cells (cDCs) because of constitutive cell-type specific expression of a suicide gene. As expected, cDC-less mice failed to mount effective T cell responses resulting in impaired viral clearance. In contrast, neither thymic negative selection nor T regulatory cell generation or T cell homeostasis were markedly affected. Unexpectedly, cDC-less mice developed a progressive myeloproliferative disorder characterized by prominent extramedullary hematopoiesis and increased serum amounts of the cytokine Flt3 ligand. Our data identify a critical role of cDCs in the control of steady-state hematopoiesis, revealing a feedback loop that links peripheral cDCs to myelogenesis through soluble growth factors, such as Flt3 ligand.