Human Dermal CD14+ Cells Are a Transient Population of Monocyte-Derived Macrophages

Summary Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141hiXCR1+CLEC9A+ DCs and CD1c+ DCs are murine CD103+ DCs and CD64−CD11b+ DCs. In addition, human tissues also contain CD14+ cells, currently designated as DCs, with an as-yet unknown murine counterpart. Here we have demonstrated that human dermal CD14+ cells are a tissue-resident population of monocyte-derived macrophages with a short half-life of <6 days. The decline and reconstitution kinetics of human blood CD14+ monocytes and dermal CD14+ cells in vivo supported their precursor-progeny relationship. The murine homologs of human dermal CD14+ cells are CD11b+CD64+ monocyte-derived macrophages. Human and mouse monocytes and macrophages were defined by highly conserved gene transcripts, which were distinct from DCs. The demonstration of monocyte-derived macrophages in the steady state in human tissue supports a conserved organization of human and mouse mononuclear phagocyte system.

[1]  R. Steinman Dendritic cells: versatile controllers of the immune system , 2007, Nature Medicine.

[2]  F. Ginhoux,et al.  Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. , 2013, Immunity.

[3]  H. Ueno,et al.  Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells. , 2008, Immunity.

[4]  F. Ginhoux,et al.  Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state , 2007, The Journal of experimental medicine.

[5]  B. Malissen,et al.  CD64 Expression Distinguishes Monocyte-Derived and Conventional Dendritic Cells and Reveals Their Distinct Role during Intramuscular Immunization , 2012, The Journal of Immunology.

[6]  Eric Vivier,et al.  Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling , 2008, Genome Biology.

[7]  Damien Chaussabel,et al.  IRF8 mutations and human dendritic-cell immunodeficiency. , 2011, The New England journal of medicine.

[8]  Michael Poidinger,et al.  Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells , 2012, Immunity.

[9]  F. Ginhoux,et al.  Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. , 2013, Immunity.

[10]  J. Pollard,et al.  A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells , 2012, Science.

[11]  B. Malissen,et al.  Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. , 2013, Immunity.

[12]  R. Russell,et al.  Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. , 2002, Blood.

[13]  B. Ryffel,et al.  Migration of Langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF‐α and IL‐1 β , 1999, Journal of leukocyte biology.

[14]  P. Rod Dunbar,et al.  Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens , 2010, The Journal of experimental medicine.

[15]  P. Kloetzel,et al.  Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells , 2010, The Journal of experimental medicine.

[16]  J. Péguet-Navarro,et al.  Differential Capacity of Human Skin Dendritic Cells to Polarize CD4+T Cells into IL-17, IL-21 and IL-22 Producing Cells , 2012, PloS one.

[17]  R. Steinman,et al.  Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. , 1998, Science.

[18]  D. Corry,et al.  Gamma-glutamyl leukotrienase, a novel endothelial membrane protein, is specifically responsible for leukotriene D(4) formation in vivo. , 2002, The American journal of pathology.

[19]  S. Akira,et al.  Identification of a key pathway required for the sterile inflammatory response triggered by dying cells , 2007, Nature Medicine.

[20]  B. Diamond,et al.  Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice , 2013, Nature Immunology.

[21]  F. Ginhoux,et al.  Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation , 2009, The Journal of experimental medicine.

[22]  P. Dunbar,et al.  Cutting Edge: CD1a+ Antigen-Presenting Cells in Human Dermis Respond Rapidly to CCR7 Ligands1 , 2006, The Journal of Immunology.

[23]  A. Thomson,et al.  CD4+ T Cell Responses Elicited by Different Subsets of Human Skin Migratory Dendritic Cells1 , 2005, The Journal of Immunology.

[24]  T. Blankenstein,et al.  CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. , 2004, Immunity.

[25]  J. Banchereau,et al.  CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha , 1996, The Journal of experimental medicine.

[26]  M. Haniffa,et al.  Rapid Detection of Dendritic Cell and Monocyte Disorders Using CD4 as a Lineage Marker of the Human Peripheral Blood Antigen-Presenting Cell Compartment , 2013, Front. Immunol..

[27]  H. Hammad,et al.  Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. , 2013, Immunity.

[28]  C. Dutertre,et al.  The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells , 2010, The Journal of experimental medicine.

[29]  F. Ginhoux,et al.  Origin of the lamina propria dendritic cell network. , 2009, Immunity.

[30]  F. Ginhoux,et al.  Ontogeny and functional specialization of dendritic cells in human and mouse. , 2013, Advances in immunology.

[31]  David H. Laidlaw,et al.  Deciphering the transcriptional network of the dendritic cell lineage - eScholarship , 2012 .

[32]  N. McGovern,et al.  The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency , 2011, The Journal of experimental medicine.

[33]  D. Corry,et al.  γ-Glutamyl Leukotrienase, a Novel Endothelial Membrane Protein, Is Specifically Responsible for Leukotriene D4 Formation in Vivo , 2002 .

[34]  V. Soumelis,et al.  Human inflammatory dendritic cells induce Th17 cell differentiation. , 2013, Immunity.

[35]  S. Nishikawa,et al.  The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene , 1990, Nature.

[36]  John P. Moore,et al.  Potent Induction of Antibody-Secreting B Cells by Human Dermal-Derived CD14+ Dendritic Cells Triggered by Dual TLR Ligation , 2012, The Journal of Immunology.

[37]  C. Thompson,et al.  Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets. , 1993, Journal of immunology.

[38]  R. van Furth,et al.  THE ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES , 1968, The Journal of experimental medicine.

[39]  B. Malissen,et al.  CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1‐inducing role of mesenteric lymph node macrophages during colitis , 2012, European journal of immunology.

[40]  Ansuman T. Satpathy,et al.  Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. , 2012, Immunity.

[41]  Steffen Jung,et al.  Intestinal lamina propria dendritic cell subsets have different origin and functions. , 2009, Immunity.

[42]  T. D. de Gruijl,et al.  A Postmigrational Switch among Skin-Derived Dendritic Cells to a Macrophage-Like Phenotype Is Predetermined by the Intracutaneous Cytokine Balance1 , 2006, The Journal of Immunology.

[43]  G. Chew House dust mite allergen. , 1996, American Industrial Hygiene Association journal.

[44]  A. Mildner,et al.  Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. , 2013, Immunity.

[45]  F. Ginhoux,et al.  Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages , 2012, The Journal of experimental medicine.

[46]  K. Williams,et al.  Immunophenotyping of lymphocyte, monocyte and dendritic cell subsets in normal rhesus macaques by 12-color flow cytometry: clarification on DC heterogeneity. , 2010, Journal of immunological methods.

[47]  Amin R. Mazloom,et al.  Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages , 2012, Nature Immunology.

[48]  N. McGovern,et al.  IRF4 Transcription Factor-Dependent CD11b+ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses , 2013, Immunity.

[49]  G. Schuler,et al.  Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization. , 1993, The Journal of clinical investigation.

[50]  N. McGovern,et al.  A Three-Dimensional Atlas of Human Dermal Leukocytes, Lymphatics, and Blood Vessels , 2013, The Journal of investigative dermatology.

[51]  B. Pulendran,et al.  Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. , 2000, Blood.

[52]  R. Steinman,et al.  Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages. , 2007, The Journal of clinical investigation.

[53]  F. Nestle,et al.  Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation , 2012, The Journal of experimental medicine.

[54]  J. Banchereau,et al.  IL-6 switches the differentiation of monocytes from dendritic cells to macrophages , 2000, Nature Immunology.

[55]  Anna M. Keller,et al.  Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells , 2010, The Journal of experimental medicine.