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HoxA10 Terminates Emergency Granulopoiesis by Increasing Expression of Triad1
- 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.
- Subjects :
- Myeloid
Ubiquitin-Protein Ligases
Immunology
Inflammation
Biology
Granulopoiesis
Article
Mice
Cell Line, Tumor
medicine
Animals
Humans
Immunology and Allergy
RNA, Messenger
Phosphorylation
Promoter Regions, Genetic
Myeloid Progenitor Cells
Homeodomain Proteins
Mice, Knockout
Myelopoiesis
Regulation of gene expression
Innate immune system
U937 cell
Ubiquitination
U937 Cells
Receptors, Fibroblast Growth Factor
Immunity, Innate
Cell biology
Mice, Inbred C57BL
Homeobox A10 Proteins
medicine.anatomical_structure
Gene Expression Regulation
Fibroblast Growth Factor 2
Bone marrow
medicine.symptom
Granulocytes
Subjects
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