Interferon consensus sequence-binding protein (Icsbp) is required for 
terminating emergency granulopoiesis, an episodic event responsible for 
granulocyte production in response to infections and a key component of the 
innate immune response. Icsbp inhibits the expression of Stat3 and C/ebpβ, 
transcription factors essential for initiating and sustaining granulopoiesis, 
and activates transcription of Fanconi C (FANCC), a DNA repair protein. In prior 
studies, we noted accelerated bone marrow failure in Fancc-/- mice undergoing 
multiple episodes of emergency granulopoiesis, associated with apoptosis of bone 
marrow cells with unrepaired DNA damage. Additionally, we found increased 
expression of Fanconi C and F proteins during emergency granulopoiesis. These 
findings suggest that Icsbp protects the bone marrow from DNA damage by 
increasing activity of the Fanconi DNA repair pathway, but the mechanisms for 
FANCC activation during initiation of emergency granulopoiesis are unclear. In 
this study, we observed that Stat3 and C/ebpβ activate FANCC transcription and 
contribute to DNA repair. Our findings indicate that FancC expression is 
increased during Stat3- and C/ebpβ-induced initiation of emergency 
granulopoiesis by these transcription factors and is maintained through 
termination by Icsbp. Our work reveals that Stat3- and C/ebpβ-mediated FancC 
expression is a critical component for initiating and sustaining key innate 
immune responses.