Emergency granulopoiesis is a component of the innate immune response that is 
induced in response to infectious or inflammatory challenge. It is characterized 
by the rapid expansion and differentiation of granulocyte/monocyte progenitor 
(GMP) populations, which is due in part to a shortened S-phase of the cell 
cycle. We found that IRF8 (also known as ICSBP), an interferon regulatory 
transcription factor that activates phagocyte effector genes during the innate 
immune response, activates the gene encoding Fanconi C (Fancc) in murine myeloid 
progenitor cells. Moreover, IRF8-induced Fancc transcription was augmented by 
treatment with IL-1β, an essential cytokine for emergency granulopoiesis. The 
Fanconi pathway participates in repair of stalled or collapsed replication forks 
during DNA replication, leading us to hypothesize that the Fanconi pathway 
contributes to genomic stability during emergency granulopoiesis. In support of 
this hypothesis, Fancc(-/-) mice developed anemia and neutropenia during 
repeated, failed episodes of emergency granulopoiesis. Failed emergency 
granulopoiesis in Fancc(-/-) mice was associated with excess apoptosis of HSCs 
and progenitor cells in the bone marrow and impaired HSC function. These studies 
have implications for understanding the pathogenesis of bone marrow failure in 
Fanconi anemia and suggest possible therapeutic approaches.