Immunity
Volume 29, Issue 6, 19 December 2008, Pages 986-997
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Article
Lack of Conventional Dendritic Cells Is Compatible with Normal Development and T Cell Homeostasis, but Causes Myeloid Proliferative Syndrome

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Summary

Dendritic cells are critically involved in the promotion and regulation of T cell responses. Here, we report a mouse strain that lacks conventional CD11chi 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.

MOLIMMUNO

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These authors contributed equally to this work

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Present address: Bayer Schering Pharma AG, 13342 Berlin, Germany