Lack of Conventional Dendritic Cells Is Compatible with Normal Development and T Cell Homeostasis, but Causes Myeloid Proliferative Syndrome

Tal Birnberg, Liat Bar-On, Anita Sapoznikov, Michele L. Caton, Luisa Cervantes-Barragán, Divine Makia, Rita Krauthgamer, Ori Brenner, Burkhard Ludewig, Damian Brockschnieder, Dieter Riethmacher, Boris Reizis, Steffen Jung

Research output: Contribution to journalArticlepeer-review

163 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)986-997
Number of pages12
JournalImmunity
Volume29
Issue number6
DOIs
Publication statusPublished - Dec 19 2008

Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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