Two Unique Human Decidual Macrophage Populations

Several important events occur at the maternal–fetal interface, including generation of maternal–fetal tolerance, remodeling of the uterine smooth muscle and its spiral arteries and glands, and placental construction. Fetal-derived extravillous trophoblasts come in direct contact with maternal decidual leukocytes. Macrophages represent ∼20% of the leukocytes at this interface. In this study, two distinct subsets of CD14+ decidual macrophages (dMɸs) are found to be present in first-trimester decidual tissue, CD11cHI and CD11cLO. Gene expression analysis by RNA microarray revealed that 379 probes were differentially expressed between these two populations. Analysis of the two subsets revealed several clusters of coregulated genes that suggest distinct functions for these subsets in tissue remodeling, growth, and development. CD11cHI dMɸs express genes associated with lipid metabolism and inflammation, whereas CD11cLO dMɸs express genes associated with extracellular matrix formation, muscle regulation, and tissue growth. The CD11cHI dMɸs also differ from CD11cLO dMɸs in their ability to process protein Ag and are likely to be the major APCs in the decidua. Moreover, these populations each secrete both proinflammatory and anti-inflammatory cytokines that may contribute to the balance that establishes fetal–maternal tolerance. Thus, they do not fit the conventional M1/M2 categorization.

[1]  H. Masuda,et al.  Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology. , 2010, Reproduction.

[2]  T. Mcclanahan,et al.  Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis , 2010, The Journal of experimental medicine.

[3]  H. Bradshaw,et al.  Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice. , 2010, The Journal of clinical investigation.

[4]  Carl Nathan,et al.  Nonresolving Inflammation , 2010, Cell.

[5]  D. Roelen,et al.  Fetal-maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells. , 2009, Journal of reproductive immunology.

[6]  J. Katz,et al.  CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids , 2009, The Journal of experimental medicine.

[7]  J. Aplin,et al.  Evidence for immune cell involvement in decidual spiral arteriole remodeling in early human pregnancy. , 2009, The American journal of pathology.

[8]  J. Strominger,et al.  HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells , 2009, Proceedings of the National Academy of Sciences.

[9]  C. Romualdi,et al.  Selection of multipotent cells and enhanced muscle reconstruction by myogenic macrophage-secreted factors. , 2009, Experimental cell research.

[10]  J. Edwards,et al.  Exploring the full spectrum of macrophage activation , 2008, Nature Reviews Immunology.

[11]  D. Koller,et al.  The Immunological Genome Project: networks of gene expression in immune cells , 2008, Nature Immunology.

[12]  G. Krikun,et al.  Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells. , 2008, The American journal of pathology.

[13]  D. Roelen,et al.  Comparison of macrophage phenotype between decidua basalis and decidua parietalis by flow cytometry. , 2008, Placenta.

[14]  S. Nelson,et al.  Prostaglandins in labor--a translational approach. , 2008, Frontiers in bioscience : a journal and virtual library.

[15]  R. Geffers,et al.  Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype , 2008, PloS one.

[16]  V. Bronte,et al.  Tumor‐induced tolerance and immune suppression by myeloid derived suppressor cells , 2008, Immunological reviews.

[17]  Jinhua Lu,et al.  The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity , 2008, Cellular and Molecular Immunology.

[18]  M. Bissell.  Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene ExpressionMartinez FO, Gordon S, Locati M, et al (Univ of Milan, Italy; Univ of Oxford, England) J Immunol 177:7303–7311, 2006§ , 2008 .

[19]  Alison S Care,et al.  Interleukin 10 Regulates Inflammatory Cytokine Synthesis to Protect Against Lipopolysaccharide-Induced Abortion and Fetal Growth Restriction in Mice1 , 2007, Biology of reproduction.

[20]  A. Sica,et al.  Altered macrophage differentiation and immune dysfunction in tumor development. , 2007, The Journal of clinical investigation.

[21]  P. Tosi,et al.  Differential Regulation of Colony Stimulating Factor 1 and Macrophage Migration Inhibitory Factor Expression by Inflammatory Cytokines in Term Human Decidua: Implications for Macrophage Trafficking at the Fetal-Maternal Interface1 , 2007, Biology of reproduction.

[22]  D. Keskin,et al.  TGFβ promotes conversion of CD16+ peripheral blood NK cells into CD16− NK cells with similarities to decidual NK cells , 2007, Proceedings of the National Academy of Sciences.

[23]  J. Hanna,et al.  Decidual NK cells regulate key developmental processes at the human fetal-maternal interface , 2006, Nature Medicine.

[24]  J. Mesirov,et al.  GenePattern 2.0 , 2006, Nature Genetics.

[25]  A. Sica,et al.  A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). , 2006, Blood.

[26]  G. Krikun,et al.  Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1beta in first trimester human decidual cells: implications for preeclampsia. , 2006, The American journal of pathology.

[27]  D. Klatzmann,et al.  CD4+CD25+ regulatory/suppressor T cells prevent allogeneic fetus rejection in mice. , 2006, Immunology letters.

[28]  A. Wagers,et al.  Cellular and Molecular Signatures of Muscle Regeneration: Current Concepts and Controversies in Adult Myogenesis , 2005, Cell.

[29]  G. Mor,et al.  Macrophages and Apoptotic Cell Clearance During Pregnancy , 2004, American journal of reproductive immunology.

[30]  A. G. Betz,et al.  Regulatory T cells mediate maternal tolerance to the fetus , 2004, Nature Immunology.

[31]  A. Moffett,et al.  The immunological paradox of pregnancy: a reappraisal. , 2004, Placenta.

[32]  A. Moffett,et al.  Dendritic Cells in the Human Decidua1 , 2003, Biology of reproduction.

[33]  M. Colonna.  TREMs in the immune system and beyond , 2003, Nature Reviews Immunology.

[34]  S. Gordon.  Alternative activation of macrophages , 2003, Nature Reviews Immunology.

[35]  S. Porcelli,et al.  Inhibition of Human NK Cell-Mediated Killing by CD1 Molecules1 , 2000, The Journal of Immunology.

[36]  B. Palanca,et al.  A critical role for murine complement regulator crry in fetomaternal tolerance. , 2000, Science.

[37]  L. Lanier,et al.  Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Leach,et al.  The Role of IL-10 in Inflammatory Bowel Disease: "Of Mice and Men" , 1999, Toxicologic pathology.

[39]  V. Fadok,et al.  Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. , 1998, The Journal of clinical investigation.

[40]  J. Baker,et al.  Effects of an Igf1 gene null mutation on mouse reproduction. , 1996, Molecular endocrinology.

[41]  S. Porcelli,et al.  Recognition of a lipid antigen by GDI-restricted αβ+ T cells , 1994, Nature.

[42]  S. Porcelli,et al.  Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. , 1994, Nature.

[43]  L. Powell-Braxton,et al.  IGF-I is required for normal embryonic growth in mice. , 1993, Genes & development.

[44]  J. S. Hunt,et al.  Antigen expression by cells near the maternal-fetal interface. , 1988, American journal of reproductive immunology and microbiology : AJRIM.