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HoxA10 Terminates Emergency Granulopoiesis by Increasing Expression of Triad1

Authors :
Ling Bei
Hao Wang
Liping Hu
Elizabeth A. Eklund
Chirag A. Shah
Source :
The Journal of Immunology. 194:5375-5387
Publication Year :
2015
Publisher :
The American Association of Immunologists, 2015.

Abstract

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.

Details

ISSN :
15506606 and 00221767
Volume :
194
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi.dedup.....a614ed632473b9e1e0fd814a4b3696f4
Full Text :
https://doi.org/10.4049/jimmunol.1401909