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 Blood, 12 November 2009, Vol. 114, No. 20, pp. 4411-4421.
Prepublished online as a Blood First Edition Paper on September 18, 2009; DOI 10.1182/blood-2008-11-188045.

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IMMUNOBIOLOGY

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

Kristin Hochweller1, Tewfik Miloud1, Jörg Striegler1, Shalin Naik2, Günter J. Hämmerling1,*, and Natalio Garbi1,*

1 Division of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; and 2 Immunology Division, The Netherlands Cancer Institute, Amsterdam, The Netherlands

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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