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

Journal of Leukocyte Biology

John Halerz¹  Andrea Szilagyi¹  Ravi Shankar  and⁴  Kirstin Howell³  Richard L. Gamelli⁴  Joseph Posluszny²  Li K. He⁴  Kuzhali Muthu ⁴ 

[1]  Burn and Shock Trauma Institute and Department of Surgery, Mount Sinai Medical Center, Chicago, Illinois, USA; Burn and Shock Trauma Institute and Department of Surgery, Case Western Reserve University, Cleveland, Ohio, USA Department of Surgery, Mount Sinai Medical Center, Chicago, Illinois, USA;;Department of Surgery, Mount Sinai Medical Center, Chicago, Illinois, USA;  Burn and Shock Trauma Institute Burn and Shock Trauma Institute and Department of Surgery, Loyola University Medical Center, Maywood, Illinois, USA;

关键词: mDC;    GMP;    M-CSF receptors;    LSK;    GATA-1;    bone marrow;   

DOI  :  10.1189/jlb.0711338

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 (Gr1negCD11b+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 Mφ 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.

【 授权许可】

Unknown