Generation of parabiotic mice for the study of DC and DC precursor circulation.

Dendritic cells (DCs) are the main regulators of adaptive immune responses and considerable interest currently focuses on the mechanisms of DC homeostasis. Understanding the mechanisms and regulation of DC generation may provide cues on how to modulate DC numbers and their longevity, an issue of wide interest in translational research. Surgical joining of the blood circulation of two mice (parabiosis) results in the equal distribution of lymphocytes between the parabiotic partners after a short period of time. In contrast, DCs fail to equalize even after prolonged periods of parabiosis suggesting that self-renewing precursors replenish mature DCs in situ. We have shown that mature DCs are constantly replenished by blood-borne precursors. Furthermore, the low but sustained exchange rate of DCs during parabiosis depends on fms-like tyrosine kinase 3 (Flt3)-mediated signals, which are important regulators for maintenance of normal DC numbers in the spleen by controlling their division in situ.