The immunophenotype of decidual macrophages in acute atherosis

Abstract

Problem: Acute atherosis is a uteroplacental arterial lesion that is associated with pregnancy complications such as preeclampsia and preterm birth, the latter being the leading cause of perinatal morbidity and mortality worldwide. However, the immunobiology of acute atherosis is poorly understood. Method of study:Placental basal plate samples were collected from women who delivered with (n = 11) and without (n = 31) decidua basalis lesions of acute atherosis.Multicolor flow cytometry was used to quantify M1-and M2-like macrophage subsets and the expression of iNOS and IL-12 by decidual macrophages. Multiplex fluorescence staining and phenoptics were performed to localize M1-, MOX-, and Mhem-like macrophages in the decidual basalis. Results:Macrophages displayed diverse phenotypes in the decidua basalis with acute atherosis. M2-like macrophages were the most abundant subset in the decidua; yet, this macrophage subset did not change with the presence of acute atherosis. Decidual M1-like macrophages were increased in acute atherosis, and such macrophages displayed a pro-inflammatory phenotype, as indicated by the expression of iNOS and IL-12. Decidual M1-like pro-inflammatory macrophages were localized near both transformed and non-transformed vessels in the decidua basalis with acute atherosis.

Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia

“…Our recent immunohistochemical investigations confirmed that perivascular infiltrates were not consistently present or large around all acute atherosis lesions and that adaptive CD4 helper T cells may be involved, whereas the presence of Tregs (FOXP3þ) was almost absent, 73 again demonstrating similarities and discrepancies relative to early atherosclerosis lesions. 92 The recent findings of a more prevalent proinflammatory macrophage phenotype in the decidua basalis with acute atherosis and an intravascular monocyte source for macrophages in acute atherosis 93 support our hypothesis that both tissue-based and circulation-based cellular pathways lead to decidual acute atherosis. 18 Similarities among the circulating biomarkers also exist between acute atherosis and atherosclerosis.…”

Regulatory T Cells Play a Role in a Subset of Idiopathic Preterm Labor/Birth and Adverse Neonatal Outcomes

“…To further explore the mechanisms whereby the loss of Tregs induces adverse perinatal outcomes, we explored the cellular repertoire at the maternal-fetal interface, in the placenta, and in the maternal circulation. This research question was based on previous studies showing that PTL involves stereotypical cellular responses at the maternal-fetal interface ( Arenas-Hernandez et al, 2016 , 2019 ; St Louis et al, 2016 ; Xu et al, 2016 ; Gomez-Lopez et al, 2017a ; Rinaldi et al, 2017 ; Garcia-Flores et al, 2018 ; Xu et al, 2018 ; Leng et al, 2019 ; Slutsky et al, 2019 ), in the placenta ( Salafia et al, 1991 ; Redline and Patterson, 1994 ; Kim et al, 2009 , 2015b ; Gill et al, 2019 ), and in the maternal circulation ( Gervasi et al, 2001 ; Pique-Regi et al, 2019 ). Foxp3 DTR dams underwent partial or total depletion of Tregs, and the decidua, myometrium, placenta, and peripheral blood were collected in preterm gestations.…”

Immunobiology of Atherosclerosis: A Complex Net of Interactions

“…Mox macrophages account for almost a third of the total macrophage content of advanced atherosclerotic plaques in mice [120,127] and play an antioxidant role dependent on their overexpression of Nrf2-related genes, such as heme oxygenase-1 ( HMOX-1 ), sulforedoxin-1 , and thioredoxin reductase [126,127,128]. Mox macrophages were initially described only in mouse models of atherosclerosis [127,129] but have since been identified in humans [130].…”