Dendritic cell (DC) development is efficiently supported by Flt3-ligand (FL) or GM-CSF in vitro, and lymphoid-organ DC maintenance in vivo is critically dependent on FL. However, the importance of GM-CSF or both cytokines for non-lymphoid organ DC homeostasis is not well defined. Here, we show that Gm-csfr and Flt3 expression in progenitor and myeloid cells correlate with the phenotype seen in the cytokine knock-out (KO) mice. Compared to wild-type, DC progenitor numbers are similar or only slightly decreased in GM-CSF-KO mice, but two-fold decreased in FL-KO mice. Spleen and lymph node cDCs are two- to three-fold reduced in GM-CSF and ten-fold reduced in FL-KO mice, while pDC numbers are only affected by FL deficiency. Epidermal DCs are equally moderately reduced, while dermal DCs are reduced to about two thirds in GM-CSF-KO and half in FL-KO mice. Compared to FL-KO mice, combined lack of GM-CSF and FL leads to a further significant reduction of DC progenitors and dermal DCs. In line with reduction of respective DCs, proliferative T cell and specific IgG responses are reduced progressively from wild-type to GM-CSF- to FL- to double-deficient mice. These data demonstrate the concerted action of GM-CSF and FL on DC maintenance.
This work was supported by the Swiss National Science Foundation and the European Commission FP6 Network of Excellence initiative (DC-THERA and MUGEN).