Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome

Birnberg, Tal, Bar-On, Liat, Sapoznikov, Anita, Caton, Michele L., Cervantes-Barragán, Luisa, Makia, Divine, Krautgamer, Rita, Brenner, Ori, Ludewig, Burkhard, Brockschnieder, Damian, Riethmacher, Dieter, Reizis, Boris and Jung, Steffan (2008) Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity, 29 (6), 986-997. (doi:10.1016/j.immuni.2008.10.012). (PMID:19062318)

Abstract

Dendritic cells are critically involved in the promotion and regulation of Tcell 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 Tcell responses resulting in impaired viral clearance. In contrast, neither thymic negative selection nor T regulatory cell generation or Tcell 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.

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Contributors

Author: Dieter Riethmacher

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