PMID- 19767511 OWN - NLM STAT- MEDLINE DCOM- 20091222 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 114 IP - 20 DP - 2009 Nov 12 TI - Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop. PG - 4411-21 LID - 10.1182/blood-2008-11-188045 [doi] AB - 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. FAU - Hochweller, Kristin AU - Hochweller K AD - Division of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Miloud, Tewfik AU - Miloud T FAU - Striegler, Jorg AU - Striegler J FAU - Naik, Shalin AU - Naik S FAU - Hammerling, Gunter J AU - Hammerling GJ FAU - Garbi, Natalio AU - Garbi N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090918 PL - United States TA - Blood JT - Blood JID - 7603509 RN - EC 2.7.10.1 (Flt3 protein, mouse) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - IM MH - Adoptive Transfer MH - Animals MH - Cell Differentiation/*immunology MH - Dendritic Cells/*cytology/immunology MH - Enzyme-Linked Immunosorbent Assay MH - Feedback, Physiological/*physiology MH - Flow Cytometry MH - Homeostasis/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Reverse Transcriptase Polymerase Chain Reaction MH - Spleen/cytology/immunology MH - Stem Cells/*cytology/immunology MH - fms-Like Tyrosine Kinase 3 EDAT- 2009/09/22 06:00 MHDA- 2009/12/23 06:00 CRDT- 2009/09/22 06:00 PHST- 2009/09/22 06:00 [entrez] PHST- 2009/09/22 06:00 [pubmed] PHST- 2009/12/23 06:00 [medline] AID - S0006-4971(20)38923-0 [pii] AID - 10.1182/blood-2008-11-188045 [doi] PST - ppublish SO - Blood. 2009 Nov 12;114(20):4411-21. doi: 10.1182/blood-2008-11-188045. Epub 2009 Sep 18.