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

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.

[1]  Ravi Shankar,et al.  Burn injury dampens erythroid cell production through reprioritizing bone marrow hematopoietic response. , 2011, The Journal of trauma.

[2]  R. Steinman,et al.  Microbial Stimulation Fully Differentiates Monocytes to DC-SIGN/CD209+ Dendritic Cells for Immune T Cell Areas , 2010, Cell.

[3]  S. Philipsen,et al.  Dynamic regulation of Gata1 expression during the maturation of conventional dendritic cells. , 2010, Experimental hematology.

[4]  Aleksandar Dakic,et al.  The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner. , 2010, Immunity.

[5]  M. Nussenzweig,et al.  Origin and development of dendritic cells , 2010, Immunological reviews.

[6]  R. Steinman,et al.  Features of the dendritic cell lineage , 2010, Immunological reviews.

[7]  Markus G. Manz,et al.  Development of Monocytes, Macrophages, and Dendritic Cells , 2010, Science.

[8]  S. Naik,et al.  Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop. , 2009, Blood.

[9]  C. Bieglmayer,et al.  Reciprocal role of GATA-1 and vitamin D receptor in human myeloid dendritic cell differentiation. , 2009, Blood.

[10]  R. Pirracchio,et al.  Monocytic HLA‐DR expression in intensive care patients: Interest for prognosis and secondary infection prediction * , 2009, Critical care medicine.

[11]  P. Kastner,et al.  MafB Restricts M-CSF-Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells , 2009, Cell.

[12]  C. Meisel,et al.  Phenotype changes and impaired function of dendritic cell subsets in patients with sepsis: a prospective observational analysis , 2009, Critical care.

[13]  Philipp S. Hoppe,et al.  Hematopoietic Cytokines Can Instruct Lineage Choice , 2009, Science.

[14]  A. Accardo-Palumbo,et al.  Circulating dendritic cells following burn. , 2009, Burns : journal of the International Society for Burn Injuries.

[15]  A. Maung,et al.  Murine dendritic cell antigen‐presenting cell function is not altered by burn injury , 2009, Journal of leukocyte biology.

[16]  D. Hume,et al.  CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation , 2009, The Journal of experimental medicine.

[17]  Francesco Ferrari,et al.  The Vitamin D3/Hox-A10 Pathway Supports MafB Function during the Monocyte Differentiation of Human CD34+ Hemopoietic Progenitors1 , 2008, The Journal of Immunology.

[18]  E. Gautier,et al.  Enhanced Dendritic Cell Survival Attenuates Lipopolysaccharide-Induced Immunosuppression and Increases Resistance to Lethal Endotoxic Shock1 , 2008, The Journal of Immunology.

[19]  R. Cox,et al.  Prophylactic Treatment with Fms-Like Tyrosine Kinase-3 Ligand after Burn Injury Enhances Global Immune Responses to Infection1 , 2008, The Journal of Immunology.

[20]  R. Gamelli,et al.  Perturbed Bone Marrow Monocyte Development Following Burn Injury and Sepsis Promote Hyporesponsive Monocytes , 2008, Journal of burn care & research : official publication of the American Burn Association.

[21]  H. Hammad,et al.  From bloodjournal.hematologylibrary.org at PENN STATE UNIVERSITY on February 22, 2013. For personal use only. , 2005 .

[22]  A. Ayala,et al.  Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: Correlation with severity and secondary septic shock , 2007, Critical care medicine.

[23]  Yong‐jun Liu,et al.  Development of dendritic-cell lineages. , 2007, Immunity.

[24]  J. D. Engel,et al.  MafB Is Essential for Renal Development and F4/80 Expression in Macrophages , 2006, Molecular and Cellular Biology.

[25]  N. Voirin,et al.  Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock , 2006, Intensive Care Medicine.

[26]  R. Zini,et al.  Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells , 2006, Cell Death and Differentiation.

[27]  Ana Cumano,et al.  A Clonogenic Bone Marrow Progenitor Specific for Macrophages and Dendritic Cells , 2006, Science.

[28]  S. Kunkel,et al.  Reversal of long-term sepsis-induced immunosuppression by dendritic cells. , 2005, Blood.

[29]  Sandrine Sarrazin,et al.  Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate. , 2005, Blood.

[30]  Masayuki Yamamoto,et al.  GATA1 Function, a Paradigm for Transcription Factors in Hematopoiesis , 2005, Molecular and Cellular Biology.

[31]  Hao Wang,et al.  Global regulation of erythroid gene expression by transcription factor GATA-1. , 2004, Blood.

[32]  R. Hotchkiss,et al.  Characterization of the Systemic Loss of Dendritic Cells in Murine Lymph Nodes During Polymicrobial Sepsis12 , 2004, The Journal of Immunology.

[33]  A. Palucka,et al.  TNF Skews Monocyte Differentiation from Macrophages to Dendritic Cells 1 , 2003, The Journal of Immunology.

[34]  R. Hotchkiss,et al.  Sepsis Induces Apoptosis and Profound Depletion of Splenic Interdigitating and Follicular Dendritic Cells1 , 2003, The Journal of Immunology.

[35]  C. Miller‐Graziano,et al.  Failure of Monocytes of Trauma Patients to Convert to Immature Dendritic Cells is Related to Preferential Macrophage-Colony-Stimulating Factor-Driven Macrophage Differentiation1 , 2003, The Journal of Immunology.

[36]  H. Macdonald,et al.  Mouse CD11c(+) B220(+) Gr1(+) plasmacytoid dendritic cells develop independently of the T-cell lineage. , 2002, Blood.

[37]  C. Coopersmith,et al.  Depletion of Dendritic Cells, But Not Macrophages, in Patients with Sepsis , 2002, The Journal of Immunology.

[38]  L. Moldawer,et al.  SEPSIS SYNDROMES: UNDERSTANDING THE ROLE OF INNATE AND ACQUIRED IMMUNITY , 2001, Shock.

[39]  R. Gamelli,et al.  Myeloid Commitment Shifts Toward Monocytopoiesis After Thermal Injury and Sepsis , 2001, Annals of surgery.

[40]  T. Graf,et al.  MafB is an inducer of monocytic differentiation , 2000, The EMBO journal.

[41]  I. Weissman,et al.  A clonogenic common myeloid progenitor that gives rise to all myeloid lineages , 2000, Nature.

[42]  C. Figdor,et al.  Generation and functional characterization of mouse monocyte‐derived dendritic cells , 1999, European journal of immunology.

[43]  B. Pulendran,et al.  Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[44]  E. Faist,et al.  SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS), MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS), MULTIPLE ORGAN FAILURE (MOF): ARE WE WINNING THE BATTLE? , 1998, Shock.

[45]  K. Shortman,et al.  Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. , 1997, Journal of immunology.

[46]  P. Holt,et al.  Brief Definitive Report Dendritic Cells Are Recruited into the Airway Epithelium during the Inflammatory Response to a Broad Spectrum of Stimuli , 2022 .

[47]  F. Lund-Johansen,et al.  Granulocytic and monocytic differentiation of CD34hi cells is associated with distinct changes in the expression of the PU.1-regulated molecules, CD64 and macrophage colony-stimulating factor receptor. , 1996, Blood.

[48]  K. Shortman,et al.  Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny , 1996, The Journal of experimental medicine.

[49]  T. Graf,et al.  MafB Is an Interaction Partner and Repressor of Ets-1 That Inhibits Erythroid Differentiation , 1996, Cell.

[50]  Michael D. Roth,et al.  Human CD14+ leukocytes acquire the phenotype and function of antigen‐presenting dendritic cells when cultured in GM‐CSF and IL‐4 , 1996, Journal of leukocyte biology.

[51]  P. Holt,et al.  Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces , 1994, The Journal of experimental medicine.

[52]  Li Wu,et al.  Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population , 1993, Nature.

[53]  R. Steinman,et al.  Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[54]  R. Steinman,et al.  Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor , 1992, The Journal of experimental medicine.

[55]  M. Mehlig,et al.  Dendritic cells from mouse bone marrow: in vitro differentiation using low doses of recombinant granulocyte-macrophage colony-stimulating factor. , 1992, Journal of immunological methods.

[56]  J. Cavaillon,et al.  Dysregulation of in vitro cytokine production by monocytes during sepsis. , 1991, The Journal of clinical investigation.

[57]  P. Morris,et al.  Migration patterns of dendritic cells in the mouse. Homing to T cell- dependent areas of spleen, and binding within marginal zone , 1988, The Journal of experimental medicine.

[58]  P. Morris,et al.  Migration patterns of dendritic cells in the mouse. , 1988, Advances in experimental medicine and biology.