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

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 maintena...

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Bibliographic Details
Published in:Blood 2009-11, Vol.114 (20), p.4411-4421
Main Authors: Hochweller, Kristin, Miloud, Tewfik, Striegler, Jörg, Naik, Shalin, Hämmerling, Günter J., Garbi, Natalio
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Biological and medical sciences
Cell Differentiation - immunology
Dendritic Cells - cytology
Dendritic Cells - immunology
Enzyme-Linked Immunosorbent Assay
Feedback, Physiological - physiology
Flow Cytometry
fms-Like Tyrosine Kinase 3
Hematologic and hematopoietic diseases
Homeostasis - immunology
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Transgenic
Reverse Transcriptase Polymerase Chain Reaction
Spleen - cytology
Spleen - immunology
Stem Cells - cytology
Stem Cells - immunology
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-11-188045