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Publication : Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop.

First Author  Hochweller K Year  2009
Journal  Blood Volume  114
Issue  20 Pages  4411-21
PubMed ID  19767511 Mgi Jnum  J:154921
Mgi Id  MGI:4411939 Doi  10.1182/blood-2008-11-188045
Citation  Hochweller K, et al. (2009) Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop. Blood 114(20):4411-21
abstractText  Dendritic cells (DCs) are key coordinators of the immune response, governing the choice between tolerance and immunity. Despite their importance, the mechanisms controlling the size of the DC compartment are largely unknown. Using a mouse model allowing continuous DC depletion, we show that maintenance of DC numbers in spleen is an active process mediated by Flt3-L-dependent regulation of precursor differentiation into DCs, rather than by changes in proliferation of the differentiated DCs. In particular, the frequency and differentiation potential of intrasplenic DC precursors increased in response to reduced DC numbers. Levels of Flt3-L, a cytokine required for DC differentiation, increased in the blood after DC depletion and returned to normal levels once the DC compartment filled up again. Our data suggest a feedback regulation of DC homeostasis whereby reduction of the DC pool size promotes differentiation of their precursors, via increased Flt3-L availability. This mechanism is different to those known for other immune cell types, such as the B- and T-cell compartments, whereby lymphopenia induces proliferation of already differentiated lymphocytes.
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