title: Modulation of Decidual Macrophage Polarization by Macrophage Colony-Stimulating Factor Derived from First-Trimester Decidual Cells: Implication in Preeclampsia.
abstract: During human pregnancy, immune tolerance of the fetal semiallograft occurs in the presence of abundant maternal leukocytes. At the implantation site, macrophages comprise approximately 20% of the leukocyte population and act as primary mediators of tissue remodeling. Decidual macrophages display a balance between anti-inflammatory and proinflammatory phenotypes. However, a shift to an M1 subtype is reported in preeclampsia. Granulocyte-macrophage colony-stimulating-factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are major differentiating factors that mediate M1 and M2 polarization, respectively. Previously, we observed the following: i) the preeclamptic decidua contains an excess of both macrophages and GM-CSF, ii) the preeclampsia-associated proinflammatory cytokines, IL-1β and tumor necrosis factor-α, markedly enhance GM-CSF and M-CSF expression in cultured leukocyte-free first-trimester decidual cells (FTDCs), iii) FTDC-secreted GM-CSF polarizes macrophages toward an M1 subtype. The microenvironment is a key determinant of macrophage phenotype. Thus, we examined proinflammatory stimulation of FTDC-secreted M-CSF and its role in macrophage development. Immunofluorescence staining demonstrated elevated M-CSF-positive decidual cell numbers in preeclamptic decidua. In FTDCs, IL-1β and tumor necrosis factor-α signal through the NF-κB pathway to induce M-CSF production, which does the following: i) enhances differentiation of and elevates CD163 expression in macrophages, ii) increases macrophage phagocytic capacity, and iii) inhibits signal-regulatory protein α expression by macrophages. These findings suggest that FTDC-secreted M-CSF modulates the decidual immune balance by inducing M2 macrophage polarization and phagocytic capacity in response to proinflammatory stimuli.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Longzhu
authors.initials: L
authors.lastname: Piao
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chang-Ching
authors.initials: CC
authors.lastname: Yeh
authors.affiliation: Department of Obstetrics and Gynecology, Beth Israel Medical Center, New York, New York.
authors.forename: Rachel
authors.initials: R
authors.lastname: Masch
authors.affiliation: Department of Obstetrics and Gynecology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, University of South Florida, College of Medicine, Tampa, Florida. Electronic address: jhuang3@health.usf.edu.
authors.forename: S Joseph
authors.initials: SJ
authors.lastname: Huang
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003656:Decidua / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000943:Antigens, Differentiation; D053583:Interleukin-1beta; D016328:NF-kappa B; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor