Expression of the E3 ubiquitin ligase Triad1 is greater in mature granulocytes 
than in myeloid progenitor cells. HoxA10 actives transcription of the gene 
encoding Triad1 (ARIH2) during myeloid differentiation, but the contribution of 
increased Triad1 expression to granulocyte production or function is unknown. 
Mice with bone marrow-specific disruption of the ARIH2 gene exhibit constitutive 
inflammation with tissue infiltration by granulocytes and B cells. In contrast, 
disruption of the HOXA10 gene in mice neither constitutively activates the 
innate immune response nor significantly alters steady-state granulopoiesis. 
This study explores the impact of HoxA10-induced Triad1 expression on emergency 
(stress) granulopoiesis. We found that mice with HOXA10 gene disruption 
exhibited an overwhelming and fatal emergency granulopoiesis response that was 
characterized by tissue infiltration with granulocytes, but reversed by 
re-expression of Triad1 in the bone marrow. We determined that HoxA9 repressed 
ARIH2 transcription in myeloid progenitor cells, antagonizing the effect of 
HoxA10 on Triad1 expression. Also, we found that differentiation-stage-specific 
ARIH2 transcription was regulated by the tyrosine phosphorylation states of 
HoxA9 and HoxA10. Our studies demonstrate a previously undescribed role for 
HoxA10 in terminating emergency granulopoiesis, suggesting an important 
contribution by Hox proteins to the innate immune response.