{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:23:05Z","timestamp":1793834585250,"version":"4.6.1"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["Doc 31-B26"],"award-info":[{"award-number":["Doc 31-B26"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Hofbauer cells (HBCs) are resident macrophages of the human placenta, regulating immune tolerance and tissue homeostasis. HBCs of a normal placenta (CTR) exhibit mainly an anti-inflammatory M2 phenotype. Under exaggerated chronic inflammation during pregnancy, as in preeclampsia (PE), a phenotypic switch towards M1 polarization has been proposed. PE, defined as maternally derived syndrome can be distinguished into two different entities: early-onset (EO) preeclampsia and late-onset (LO) preeclampsia. Although the clinical presenting characteristics overlap, both can be identified by biochemical markers, heritability, and different maternal and fetal outcomes. To date, no study has specifically investigated polarization and phenotype of EO- and LO-PE HBCs and looked at possible changes in HBC functionality. Primary HBCs were isolated from CTR and PE placentae. First,\n                    <jats:italic>in vitro<\/jats:italic>\n                    morphological differences were observed between CTR and PE HBCs, with both PE groups exhibiting features of M1 macrophages alongside M2 forms. Interestingly, a different polarization pattern was observed between EO- and LO-PE HBCs. EO-PE HBCs develop a tissue remodeling M2 phenotype that is strongly shifted toward M1 polarization and showed a significant upregulation of CD86, TLR4, and HLA-DR. Furthermore, this pro-inflammatory signature is corroborated by higher expression of IRF5 and of\n                    <jats:italic>NOS2<\/jats:italic>\n                    (p \u2264 0.05). However, their M2 characteristics is reflected by significant TGF-\u03b2 secretion and\n                    <jats:italic>ARG1<\/jats:italic>\n                    expression. In contrast, LO-PE HBCs developed a phagocytic CD209-low M2 phenotype in which the M1 pattern was not as pronounced as they downregulated the\n                    <jats:italic>NOS2<\/jats:italic>\n                    gene, but expressed increased levels of pro-inflammatory CD80 and TLR1 (p \u2264 0.05). The enhanced phagocytosis and MMP-9 secretion alongside the increased secretion of anti-inflammatory IL -4, IL -13 and TGF-\u03b2 in both EO- and LO-PE HBCs suggests their adaptive role and plasticity in resolving inflammation and tissue homeostasis.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.1095879","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T02:02:38Z","timestamp":1673488958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":45,"title":["Placental macrophages present distinct polarization pattern and effector functions depending on clinical onset of preeclampsia"],"prefix":"10.3389","volume":"13","author":[{"given":"Monika Horvat","family":"Mercnik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Schliefsteiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Fluhr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Wadsack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000003891","article-title":"Gestational hypertension and preeclampsia: ACOG practice bulletin, number 222","volume":"135","year":"2020","journal-title":"Obstet Gynecol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000003020","article-title":"203: Chronic hypertension in pregnancy","volume":"133","author":"Practice Bulletin No","year":"2019","journal-title":"Obstet Gynecol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1161\/HYPERTENSIONAHA.117.10803","article-title":"Hypertensive disorders of pregnancy","volume":"72","author":"Brown","year":"2018","journal-title":"Hypertension"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4108271","article-title":"Early-and late-onset preeclampsia: A comprehensive cohort study of laboratory and clinical findings according to the new ISHHP criteria","volume":"2019","author":"W\u00f3jtowicz","year":"2019","journal-title":"Int J Hypertens"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1081\/PRG-120021060","article-title":"Subclassification of preeclampsia","volume":"22","author":"von Dadelszen","year":"2003","journal-title":"Hypertens Pregnancy"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/J.PREGHY.2012.11.001","article-title":"The definition of severe and early-onset preeclampsia. statements from the international society for the study of hypertension in pregnancy (ISSHP)","volume":"3","author":"Tranquilli","year":"2013","journal-title":"Pregnancy Hypertension: Int J Women\u2019s Cardiovasc Health"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.107607","article-title":"Placental origins of preeclampsia: Challenging the current hypothesis","volume":"51","author":"Huppertz","year":"2008","journal-title":"Hypertension"},{"key":"B8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/J.PREGHY.2015.12.003","article-title":"An analysis of the differences between early and late preeclampsia with severe hypertension","volume":"6","author":"Li","year":"2016","journal-title":"Pregnancy Hypertension: Int J Women\u2019s Cardiovasc Health"},{"key":"B9","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/J.AJOG.2013.09.010","article-title":"Placental pathology suggesting that preeclampsia is more than one disease","volume":"210","author":"Nelson","year":"2014","journal-title":"Am J Obstet Gynecol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/J.AJOG.2013.07.030","article-title":"Patterns of maternal vascular remodeling and responsiveness in early- versus late-onset preeclampsia","volume":"209","author":"Stergiotou","year":"2013","journal-title":"Am J Obstet Gynecol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031019","article-title":"Sphingolipid signature of human feto-placental vasculature in preeclampsia","volume":"21","author":"del Gaudio","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS21041406","article-title":"Inflammasomes\u2013a molecular link for altered immunoregulation and inflammation mediated vascular dysfunction in preeclampsia","volume":"21","author":"Murthi","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/J.SINY.2006.04.001","article-title":"Inflammation and pre-eclampsia","volume":"11","author":"Borzychowski","year":"2006","journal-title":"Semin Fetal Neonatal Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/J.1600-0897.2007.00486.X","article-title":"Leptin, IL-10 and inflammatory markers (TNF-\u03b1, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women","volume":"58","author":"Sharma","year":"2007","journal-title":"Am J Reprod Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2021.01.011","article-title":"Preeclampsia: inflammatory signature of decidual cells in early manifestation of disease","volume":"104","author":"Vishnyakova","year":"2021","journal-title":"Placenta"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.01864\/XML\/NLM","article-title":"Mechanisms of key innate immune cells in early- and late-onset preeclampsia","volume":"11","author":"Aneman","year":"2020","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2019.01305\/BIBTEX","article-title":"Differential dynamics of the maternal immune system in healthy pregnancy and preeclampsia","volume":"10","author":"Han","year":"2019","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2021.780043\/BIBTEX","article-title":"The placental innate immune system is altered in early-onset preeclampsia, but not in late-onset preeclampsia","volume":"12","author":"Broekhuizen","year":"2021","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000015080","article-title":"Immune imbalance is associated with the development of preeclampsia","volume":"98","author":"Ma","year":"2019","journal-title":"Med (United States)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS19061801","article-title":"Role of human macrophage polarization in inflammation during infectious diseases","volume":"19","author":"Atri","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Shapouri-Moghaddam","year":"2018","journal-title":"J Cell Physiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/J.IMMUNI.2014.01.006","article-title":"Transcriptome-based network analysis reveals a spectrum model of human macrophage activation","volume":"40","author":"Xue","year":"2014","journal-title":"Immunity"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-87720-y","article-title":"Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures","volume":"11","author":"Takiguchi","year":"2021","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/J.1365-2249.2005.02934.X","article-title":"Macrophage activation switching: an asset for the resolution of inflammation","volume":"142","author":"Porcheray","year":"2005","journal-title":"Clin Exp Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-73624-w","article-title":"M1 macrophage and M1\/M2 ratio defined by transcriptomic signatures resemble only part of their conventional clinical characteristics in breast cancer","volume":"10","author":"Oshi","year":"2020","journal-title":"Sci Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1530\/REP-16-0159","article-title":"Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis","volume":"152","author":"Loegl","year":"2016","journal-title":"Reproduction"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 paradigm of macrophage activation: time for reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000Prime Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1242\/DEV.163428","article-title":"Development of the human placenta","volume":"146","author":"Turco","year":"2019","journal-title":"Development"},{"key":"B29","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/978-3-319-54090-0_3","article-title":"\u201cHofbauer cells: Placental macrophages of fetal origin\u201d","volume":"62","author":"Reyes","year":"2017","journal-title":"Results Problems Cell Differentiation"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030736","article-title":"Placental hofbauer cell polarization resists inflammatory cues In vitro","volume":"21","author":"Schliefsteiner","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00888","article-title":"Human placental hofbauer cells maintain an anti-inflammatory M2 phenotype despite the presence of gestational diabetes mellitus","volume":"8","author":"Schliefsteiner","year":"2017","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1210\/EN.2012-1575","article-title":"Glucocorticoids enhance CD163 expression in placental hofbauer cells","volume":"154","author":"Tang","year":"2013","journal-title":"Endocrinology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/J.1600-0897.2012.01108.X","article-title":"Methylome of fetal and maternal monocytes and macrophages at the feto-maternal interface","volume":"68","author":"Kim","year":"2012","journal-title":"Am J Reprod Immunol"},{"key":"B34","unstructured":"The phenotype of human placental macrophages and its variation with gestational age\n            GoldsteinJ\n            BravermanM\n            SalafiaC\n            BuckleyP\n          1988"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1159\/000497416","article-title":"The elusive role of placental macrophages: The hofbauer cell","volume":"11","author":"Zulu","year":"2019","journal-title":"J Innate Immun"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e20200891","DOI":"10.1084\/JEM.20200891","article-title":"Phenotypic and functional characterization of first-trimester human placental macrophages, hofbauer cells","volume":"218","author":"Thomas","year":"2020","journal-title":"J Exp Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/aji.12336","article-title":"Toll-like receptor-mediated responses by placental hofbauer cells (HBCs): A potential pro-inflammatory role for fetal M2 macrophages","volume":"73","author":"Young","year":"2015","journal-title":"Am J Reprod Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.1401536","article-title":"The human fetal placenta promotes tolerance against the semiallogeneic fetus by inducing regulatory T cells and homeostatic M2 macrophages","volume":"194","author":"Svensson-Arvelund","year":"2015","journal-title":"J Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/S004410051236","article-title":"Paracrine regulation of distinct trophoblast functions in vitro by placental macrophages","volume":"295","author":"Cervar","year":"1999","journal-title":"Cell Tissue Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1095\/BIOLREPROD62.4.1075","article-title":"Human villous macrophage-conditioned media enhance human trophoblast growth and differentiation","volume":"62","author":"Khan","year":"2000","journal-title":"In Vitro Biol Reprod"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/J.PLACENTA.2004.08.008","article-title":"Human placental hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching","volume":"26","author":"Anteby","year":"2005","journal-title":"Placenta"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/J.PLACENTA.2007.01.010","article-title":"Hofbauer cells in early human placenta: possible implications in vasculogenesis and angiogenesis","volume":"28","author":"Seval","year":"2007","journal-title":"Placenta"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300988","article-title":"Placental macrophages are impaired in chorioamnionitis, an infectious pathology of the placenta","volume":"191","author":"ben Amara","year":"2013","journal-title":"J Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.2350\/09-03-0632-OA.1","article-title":"The number of CD68+ (Hofbauer) cells is decreased in placentas with chorioamnionitis and with advancing gestational age","volume":"13","author":"Vinnars","year":"2010","journal-title":"Pediatr Dev Pathol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2010.00927.x","article-title":"Focal increases of fetal macrophages in placentas from pregnancies with histological chorioamnionitis: Potential role of fibroblast monocyte chemotactic protein-1","volume":"65","author":"Toti","year":"2011","journal-title":"Am J Reprod Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2008.02964.x","article-title":"Involvement of hofbauer cells and maternal T cells in villitis of unknown aetiology","volume":"52","author":"Kim","year":"2008","journal-title":"Histopathology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/J.CHOM.2016.05.015","article-title":"Zika virus infects human placental macrophages","volume":"20","author":"Quicke","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2011.01006.x","article-title":"Isolation of hofbauer cells from human term placentas with high yield and purity","volume":"66","author":"Tang","year":"2011","journal-title":"Am J Reprod Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1067\/S0002-9378(03)00576-3","article-title":"The frequency and severity of placental findings in women with preeclampsia are gestational age dependent","volume":"189","author":"Moldenhauer","year":"2003","journal-title":"Am J Obstet Gynecol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/AJI.12112","article-title":"Decreased levels of folate receptor-\u03b2 and reduced numbers of fetal macrophages (Hofbauer cells) in placentas from pregnancies with severe pre-eclampsia","volume":"70","author":"Tang","year":"2013","journal-title":"Am J Reprod Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.1308887110","article-title":"Modulation of macrophage phenotype by cell shape","volume":"110","author":"McWhorter","year":"2013","journal-title":"Proc Natl Acad Sci"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/J.SMIM.2015.10.003","article-title":"Molecular and epigenetic basis of macrophage polarized activation","volume":"27","author":"Porta","year":"2015","journal-title":"Semin Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RU1018-378RR","article-title":"M2b macrophage polarization and its roles in diseases","volume":"106","author":"Wang","year":"2019","journal-title":"J Leukoc Biol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.2741\/2692\/PDF","article-title":"Macrophage activation and polarization","volume":"13","author":"Martinez","year":"2008","journal-title":"Front Bioscience"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.0508327102","article-title":"Negative regulation of toll-like-receptor signaling by IRF-4","volume":"102","author":"Negishi","year":"2005","journal-title":"Proc Natl Acad Sci"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nature03308","article-title":"Integral role of IRF-5 in the gene induction programme activated by toll-like receptors","volume":"434","author":"Takaoka","year":"2005","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1990","article-title":"IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses","volume":"12","author":"Krausgruber","year":"2011","journal-title":"Nat Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.0504226102","article-title":"Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS","volume":"102","author":"Honma","year":"2005","journal-title":"Proc Natl Acad Sci"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2017.01097","article-title":"Regulation of human macrophage M1\u2013M2 polarization balance by hypoxia and the triggering receptor expressed on myeloid cells-1","author":"Raggi","year":"2017","journal-title":"Front Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1093\/INTIMM\/DXU090","article-title":"IL-10 enhances the phenotype of M2 macrophages induced by IL-4 and confers the ability to increase eosinophil migration","volume":"27","author":"Makita","year":"2015","journal-title":"Int Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0094188","article-title":"The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages","volume":"9","author":"Fernando","year":"2014","journal-title":"PloS One"},{"key":"B63","doi-asserted-by":"publisher","first-page":"H926","DOI":"10.1152\/AJPHEART.00779.2008","article-title":"ICAM-1: role in inflammation and in the regulation of vascular permeability","volume":"295","author":"Frank","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-21066-x","article-title":"High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming","volume":"12","author":"Hu","year":"2021","journal-title":"Nat Commun"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduction Targeted Ther"},{"key":"B66","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/J.IMMUNI.2014.06.008","article-title":"Macrophage activation and polarization: Nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"B67","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1177\/0022034512437372","article-title":"Control of cytokine mRNA expression by RNA-binding proteins and microRNAs","volume":"91","author":"Palanisamy","year":"2012","journal-title":"J Dent Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2014.00532","article-title":"Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages","author":"Rath","year":"2014","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/cr.2013.75","article-title":"ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages","volume":"23","author":"Zhang","year":"2013","journal-title":"Cell Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMBIO.2018.11.010","article-title":"Reactive oxygen species (ROS) in macrophage activation and function in diabetes","volume":"224","author":"Rendra","year":"2019","journal-title":"Immunobiology"},{"key":"B71","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/J.FREERADBIOMED.2019.12.018","article-title":"Scavenging reactive oxygen species selectively inhibits M2 macrophage polarization and their pro-tumorigenic function in part, via Stat3 suppression","volume":"147","author":"Griess","year":"2020","journal-title":"Free Radic Biol Med"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41420-019-0146-x","article-title":"Three cell deaths and a funeral: macrophage clearance of cells undergoing distinct modes of cell death","volume":"5","author":"Kl\u00f6ditz","year":"2019","journal-title":"Cell Death Discov"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02628","article-title":"Hofbauer cells: Their role in healthy and complicated pregnancy","volume":"9","author":"Reyes","year":"2018","journal-title":"Front Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00098","article-title":"Immune and apoptosis mechanisms regulating placental development and vascularization in preeclampsia","volume":"11","author":"Raguema","year":"2020","journal-title":"Front Physiol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0119-6","article-title":"Pre-eclampsia: pathogenesis, novel diagnostics and therapies","volume":"15","author":"Phipps","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/J.BBAMCR.2010.01.003","article-title":"The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity","volume":"1803","author":"Brew","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700063","article-title":"Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics","volume":"84","author":"Cataldo","year":"2004","journal-title":"Lab Invest"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000070112.80711.3D","article-title":"Matrix metalloproteinases and tissue inhibitors of metalloproteinases","volume":"92","author":"Visse","year":"2003","journal-title":"Circ Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1080\/09638280701785395","article-title":"The effect of stress-deprivation and cyclic loading on the TIMP\/MMP ratio in tendon cells: An in vitro experimental study","volume":"30","author":"Gardner","year":"2008","journal-title":"Disabil Rehabil"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/J.MATBIO.2015.03.005","article-title":"The role of TIMPs in regulation of extracellular matrix proteolysis","author":"Arpino","year":"2015","journal-title":"Matrix Biol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.1100130","article-title":"Macrophages at the fetal\u2013maternal interface express markers of alternative activation and are induced by m-CSF and IL-10","volume":"187","author":"Svensson","year":"2011","journal-title":"J Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313276\/FORMAT\/EPUB","article-title":"Preeclampsia: Pathophysiology, challenges, and perspectives","volume":"124","author":"Rana","year":"2019","journal-title":"Circ Res"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.7150\/THNO.56141","article-title":"Distinct placental molecular processes associated with early-onset and late-onset preeclampsia","volume":"11","author":"Ren","year":"2021","journal-title":"Theranostics"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1002\/PD.3872","article-title":"The placental component in early-onset and late-onset preeclampsia in relation to fetal growth restriction","volume":"32","author":"Kovo","year":"2012","journal-title":"Prenat Diagn"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/J.PLACENTA.2014.01.008","article-title":"Placental perfusion in normal pregnancy and early and late preeclampsia: A magnetic resonance imaging study","volume":"35","author":"Sohlberg","year":"2014","journal-title":"Placenta"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBADIS.2020.165961","article-title":"Oxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia","volume":"1866","author":"Mar\u00edn","year":"2020","journal-title":"Biochim Biophys Acta (BBA) - Mol Basis Dis"},{"key":"B87","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/J.MAM.2007.02.006","article-title":"The role of the immune system in preeclampsia","volume":"28","author":"Saito","year":"2007","journal-title":"Mol Aspects Med"},{"key":"B88","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0002-9440(10)65123-1","article-title":"Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall","volume":"155","author":"DiFederico","year":"1999","journal-title":"Am J Pathol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0059609","article-title":"Abnormal apoptosis of trophoblastic cells is related to the up-regulation of CYP11A gene in placenta of preeclampsia patients","volume":"8","author":"He","year":"2013","journal-title":"PloS One"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1477-7827-1-119\/FIGURES\/4","article-title":"Potential role of macrophages as immunoregulators of pregnancy","volume":"1","author":"Mor","year":"2003","journal-title":"Reprod Biol Endocrinol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/J.PLACENTA.2011.02.003","article-title":"Placental macrophage (Hofbauer cell) polarization is independent of maternal allergen-sensitization and presence of chorioamnionitis","volume":"32","author":"Joerink","year":"2011","journal-title":"Placenta"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1920","article-title":"The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection","volume":"11","author":"Satoh","year":"2010","journal-title":"Nat Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/J.AJOG.2005.07.076","article-title":"Toll-like receptor 4: A potential link between \u201cdanger signals,\u201d the innate immune system, and preeclampsia","volume":"193","author":"Yeon","year":"2005","journal-title":"Am J Obstet Gynecol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.1914742117\/-\/DCSUPPLEMENTAL","article-title":"Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes","volume":"117","author":"al Mamun","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMBIO.2010.05.031","article-title":"Interleukin-4 induced interferon regulatory factor (Irf) 4 participates in the regulation of alternative macrophage priming","volume":"215","author":"el Chartouni","year":"2010","journal-title":"Immunobiology"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/J.JRI.2017.09.012","article-title":"DC-SIGN expression in hofbauer cells may play an important role in immune tolerance in fetal chorionic villi during the development of preeclampsia","volume":"124","author":"Yang","year":"2017","journal-title":"J Reprod Immunol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.1103180","article-title":"IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration","volume":"189","author":"Deng","year":"2012","journal-title":"J Immunol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1006\/CYTO.2000.0720","article-title":"Human monocytes express cd163, which is upregulated by il-10 and identical TO p155","volume":"12","author":"Sulahian","year":"2000","journal-title":"Cytokine"},{"key":"B99","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/J.GENE.2005.04.004","article-title":"Induction of arginase I transcription by IL-4 requires a composite DNA response element for STAT6 and C\/EBP\u03b2","volume":"353","author":"Gray","year":"2005","journal-title":"Gene"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/J.AJPATH.2015.04.013","article-title":"IL-4 regulates specific arg-1+ macrophage sFlt-1\u2013mediated inhibition of angiogenesis","volume":"185","author":"Wu","year":"2015","journal-title":"Am J Pathol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.169.5.2253","article-title":"Shaping gene expression in activated and resting primary macrophages by IL-10","volume":"169","author":"Lang","year":"2002","journal-title":"J Immunol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.274.45.31868","article-title":"Interleukin-10 signaling blocks inhibitor of \u03baB kinase activity and nuclear factor \u03baB DNA binding *","volume":"274","author":"Schottelius","year":"1999","journal-title":"J Biol Chem"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3829","article-title":"Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity","volume":"21","author":"Dalmas","year":"2015","journal-title":"Nat Med"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00541-3","article-title":"Macrophages and the maintenance of homeostasis","volume":"18","author":"Mosser","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMMUNI.2009.06.018","article-title":"Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR","volume":"31","author":"A-Gonzalez","year":"2009","journal-title":"Immunity"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.00553\/BIBTEX","article-title":"Phagocytosis of apoptotic cells in resolution of inflammation","volume":"11","author":"Kourtzelis","year":"2020","journal-title":"Front Immunol"},{"key":"B107","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2172-13-31","article-title":"TGF\u03b2 signaling plays a critical role in promoting alternative macrophage activation","volume":"13","author":"Gong","year":"2012","journal-title":"BMC Immunol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1093\/INTIMM\/DXY054","article-title":"Macrophages in inflammation, repair and regeneration","volume":"30","author":"Oishi","year":"2018","journal-title":"Int Immunol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M111.290676\/ATTACHMENT\/13099993-EBF4-49E0-A71C-77C3089A9E06\/MMC1.PDF","article-title":"Classically activated macrophages use stable microtubules for matrix metalloproteinase-9 (MMP-9) secretion","volume":"287","author":"Hanania","year":"2012","journal-title":"J Biol Chem"},{"key":"B110","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41413-017-0005-4","article-title":"Transforming growth factor-\u03b2 in stem cells and tissue homeostasis","volume":"6","author":"Xu","year":"2018","journal-title":"Bone Res"},{"key":"B111","doi-asserted-by":"publisher","first-page":"L1006","DOI":"10.1152\/AJPLUNG.00015.2014","article-title":"Matrix metalloproteinase-9 activates TGF-\u03b2 and stimulates fibroblast contraction of collagen gels","volume":"306","author":"Kobayashi","year":"2014","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1182\/BLOOD-2013-05-501494","article-title":"Angiogenic capacity of M1- and M2-polarized macrophages is determined by the levels of TIMP-1 complexed with their secreted proMMP-9","volume":"1122","author":"Zajac","year":"2013","journal-title":"Blood"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1095879\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T02:02:45Z","timestamp":1673488965000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1095879\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,12]]},"references-count":112,"alternative-id":["10.3389\/fimmu.2022.1095879"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1095879","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,12]]},"article-number":"1095879"}}