High MafB expression following burn augments monocyte commitment and inhibits DC differentiation in hemopoietic progenitors Journal Article

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Authors: Howell, K.; Posluszny, J; He, L. K.; Szilagyi, A.; Halerz, J.; Gamelli, R. L.; Shankar, R.; Muthu, K.
Article Title: High MafB expression following burn augments monocyte commitment and inhibits DC differentiation in hemopoietic progenitors
Abstract: We have previously shown that perturbed bone marrow progenitor development promotes hyporesponsive monocytes following experimental burn sepsis. Clinical and experimental sepsis is associated with monocyte deactivation and depletion of mDCs. Decrease in circulating DCs is reported in burn patients who develop sepsis. In our 15% TBSA scald burn model, we demonstrate a significant reduction in the circulating MHC-II(+) population and mDCs (Gr1(neg)CD11b(+)CD11c(+)) with a corresponding decrease in bone marrow MHC-II(+) cells and mDCs for up to 14 days following burn. We explored the underlying mechanism(s) that regulate bone marrow development of monocytes and DCs following burn injury. We found a robust bone marrow response with a significant increase in multipotential HSCs (LSK) and bipotential GMPs following burn injury. GMPs from burn mice exhibit a significant reduction in GATA-1, which is essential for DC development, but express high levels of MafB and M-CSFRs, both associated with monocyte production. GMPs obtained from burn mice differentiated 1.7 times more into Mvarphi and 1.6-fold less into DCs compared with sham. Monocytes and DCs expressed 50% less MHC-II in burn versus sham. Increased monocyte commitment in burn GMPs was a result of high MafB and M-CSFR expressions. Transient silencing of MafB (siRNA) in GMP-derived monocytes from burn mice partially restored DC differentiation deficits and increased GATA-1 expression. We provide evidence that high MafB following burn plays an inhibitory role in monocyte-derived DC differentiation by regulating M-CSFR and GATA-1 expressions.
Journal Title: Journal of leukocyte biology
Volume: 91
Issue: 1
ISSN: 1938-3673; 0741-5400
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 69
End Page: 81
Language: eng
DOI/URL:

10.1189/jlb.0711338

10.1189/jlb.0711338
Notes: LR: 20130523; GR: R01 GM 42577/GM/NIGMS NIH HHS/United States; GR: R03 AI 079530-01/AI/NIAID NIH HHS/United States; JID: 8405628; 0 (GATA1 Transcription Factor); 0 (Gata1 protein, mouse); 0 (Growth Inhibitors); 0 (MafB Transcription Factor); 0 (Mafb protein, mouse); EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor); OID: NLM: PMC3250307; 2011/10/07 [aheadofprint]; ppublish