Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 May 1

PMID 18446208

Citations 164

Authors

Charlotte Gustafsson

Jenny Mjosberg

Andreas Matussek

Robert Geffers

Leif Matthiesen

Goran Berg

Surendra Sharma

Jan Buer

Jan Ernerudh

Affiliations

Soon will be listed here.

Abstract

Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known.

Methodology/principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications.

Conclusions/significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.

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References

Coolman M, de Maat M, van Heerde W, Felida L, Schoormans S, Steegers E . Matrix metalloproteinase-9 gene -1562C/T polymorphism mitigates preeclampsia. Placenta. 2006; 28(7):709-13. DOI: 10.1016/j.placenta.2006.06.017. View

Takahashi K, Rochford C, Neumann H . Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med. 2005; 201(4):647-57. PMC: 2213053. DOI: 10.1084/jem.20041611. View

Parhar R, Kennedy T, Lala P . Suppression of lymphocyte alloreactivity by early gestational human decidua. I. Characterization of suppressor cells and suppressor molecules. Cell Immunol. 1988; 116(2):392-410. DOI: 10.1016/0008-8749(88)90240-7. View

Baykal C, Guler G, Al A, Tulunay G, Ozer S, Yencilek R . Expression of hepatocyte growth factor/scatter factor receptor in IUGR fetuses' placentas: an immunohistochemical analysis. Fetal Diagn Ther. 2005; 20(4):249-53. DOI: 10.1159/000085079. View

Mizuno M, Aoki K, Kimbara T . Functions of macrophages in human decidual tissue in early pregnancy. Am J Reprod Immunol. 1994; 31(4):180-8. DOI: 10.1111/j.1600-0897.1994.tb00865.x. View

Lewis C, Pollard J . Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006; 66(2):605-12. DOI: 10.1158/0008-5472.CAN-05-4005. View

Sacks G, Clover L, Bainbridge D, Redman C, Sargent I . Flow cytometric measurement of intracellular Th1 and Th2 cytokine production by human villous and extravillous cytotrophoblast. Placenta. 2001; 22(6):550-9. DOI: 10.1053/plac.2001.0686. View

Bischof R, Zafiropoulos D, Hamilton J, Campbell I . Exacerbation of acute inflammatory arthritis by the colony-stimulating factors CSF-1 and granulocyte macrophage (GM)-CSF: evidence of macrophage infiltration and local proliferation. Clin Exp Immunol. 2000; 119(2):361-7. PMC: 1905504. DOI: 10.1046/j.1365-2249.2000.01125.x. View

Marvin K, Keelan J, Eykholt R, Sato T, Mitchell M . Use of cDNA arrays to generate differential expression profiles for inflammatory genes in human gestational membranes delivered at term and preterm. Mol Hum Reprod. 2002; 8(4):399-408. DOI: 10.1093/molehr/8.4.399. View

10.

Furugori K, Kurauchi O, Itakura A, Kanou Y, Murata Y, Mizutani S . Levels of hepatocyte growth factor and its messenger ribonucleic acid in uncomplicated pregnancies and those complicated by preeclampsia. J Clin Endocrinol Metab. 1997; 82(8):2726-30. DOI: 10.1210/jcem.82.8.4176. View

11.

Rieger L, Hofmeister V, Probe C, Dietl J, Weiss E, Steck T . Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E. Mol Hum Reprod. 2002; 8(3):255-61. DOI: 10.1093/molehr/8.3.255. View

12.

Larin S, Gorlina N, Kozlov I, Cheredeev A, Zorin N, Zorina R . Binding of alpha2-macroglobulin to collagen type I: modification of collagen matrix by alpha2-macroglobulin induces the enhancement of macrophage migration. Russ J Immunol. 2003; 7(1):34-40. View

13.

Laskarin G, Cupurdija K, Sotosek Tokmadzic V, Dorcic D, Dupor J, Juretic K . The presence of functional mannose receptor on macrophages at the maternal-fetal interface. Hum Reprod. 2005; 20(4):1057-66. DOI: 10.1093/humrep/deh740. View

14.

Roth I, Corry D, Locksley R, Abrams J, Litton M, Fisher S . Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10. J Exp Med. 1996; 184(2):539-48. PMC: 2192727. DOI: 10.1084/jem.184.2.539. View

15.

Kammerer U, Eggert A, Kapp M, McLellan A, Geijtenbeek T, Dietl J . Unique appearance of proliferating antigen-presenting cells expressing DC-SIGN (CD209) in the decidua of early human pregnancy. Am J Pathol. 2003; 162(3):887-96. PMC: 1868095. DOI: 10.1016/S0002-9440(10)63884-9. View

16.

Volpe E, Cappelli G, Grassi M, Martino A, Serafino A, Colizzi V . Gene expression profiling of human macrophages at late time of infection with Mycobacterium tuberculosis. Immunology. 2006; 118(4):449-60. PMC: 1782319. DOI: 10.1111/j.1365-2567.2006.02378.x. View

17.

Hamerman J, Jarjoura J, Humphrey M, Nakamura M, Seaman W, Lanier L . Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol. 2006; 177(4):2051-5. DOI: 10.4049/jimmunol.177.4.2051. View

18.

Aoki S, Hata T, Manabe A, Miyazaki K . Decreased maternal circulating hepatocyte growth factor (HGF) concentrations in pregnancies with small for gestational age infants. Hum Reprod. 1998; 13(1O):2950-3. DOI: 10.1093/humrep/13.10.2950. View

19.

Gustafsson C, Hummerdal P, Matthiesen L, Berg G, Ekerfelt C, Ernerudh J . Cytokine secretion in decidual mononuclear cells from term human pregnancy with or without labour: ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha. J Reprod Immunol. 2006; 71(1):41-56. DOI: 10.1016/j.jri.2005.12.009. View

20.

Chaouat G, Cayol V, Mairovitz V, Dubanchet S . Localization of the Th2 cytokines IL-3, IL-4, IL-10 at the fetomaternal interface during human and murine pregnancy and lack of requirement for Fas/Fas ligand interaction for a successful allogeneic pregnancy. Am J Reprod Immunol. 1999; 42(1):1-13. DOI: 10.1111/j.1600-0897.1999.tb00459.x. View