A molecular explanation for the reciprocal effects of GM-CSF and Flt3L on DC immunogenicity. The complementary effects GM-CSF and Flt3L have on the DCs they generate can be explained by their molecular actions. Through activation of STAT3, Flt3L promotes expression of IDO but inhibits canonical NF-κB and MHC class II expression, thereby inhibiting DC immunogenicity. In contrast, GM-CSF activates STAT5 and canonical NF-κB besides STAT3. By promoting NF-κB activity and MHC class II expression, STAT5 overrules the tolerogenic function of STAT3, resulting in the development of more immunogenic DCs.