The immunophenotype of decidual macrophages in acute atherosis.

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. MOX and Mhem macrophages were also identified near transformed vessels in the decidua basalis with acute atherosis. Finally, monocyte-like cells were present on the vessel wall of non-transformed decidual vessels, indicating a possible intravascular source for macrophages in acute atherosis. CONCLUSION: Decidual macrophages display different phenotypes, namely M1-like, M2-like, MOX, and Mhem subsets. Yet, pro-inflammatory macrophages are enriched in the decidua basalis with acute atherosis. These findings provide a molecular foundation for future mechanistic inquiries about the role of pro-inflammatory macrophages in the pathogenesis of acute atherosis.

Innate lymphoid cells at the human maternal-fetal interface in spontaneous preterm labor.

PROBLEM: Pathological inflammation is causally linked to preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Our aims were to investigate whether (i) the newly described family of innate lymphoid cells (ILCs) was present at the human maternal-fetal interface and (ii) ILC inflammatory subsets were associated with the pathological process of preterm labor. METHODS OF STUDY: Decidual leukocytes were isolated from women with preterm or term labor as well as from gestational age-matched non-labor controls. ILCs (CD15- CD14- CD3- CD19- CD56- CD11b- CD127+ cells) and their subsets (ILC1, T-bet+ ILCs; ILC2, GATA3+ ILCs; and ILC3, RORγt+ ILCs) and cytokine expression were identified in the decidual tissues using immunophenotyping. RESULTS: (i) The proportion of total ILCs was increased in the decidua parietalis of women with preterm labor; (ii) ILC1s were a minor subset of decidual ILCs during preterm and term gestations; (iii) ILC2s were the most abundant ILC subset in the decidua during preterm and term gestations; (iv) the proportion of ILC2s was increased in the decidua basalis of women with preterm labor; (v) the proportion of ILC3s was increased in the decidua parietalis of women with preterm labor; and (vi) during preterm labor, ILC3s had higher expression of IL-22, IL-17A, IL-13, and IFN-γ compared to ILC2s in the decidua. CONCLUSION: ILC2s were the most abundant ILC subset at the human maternal-fetal interface during preterm and term gestations. Yet, during preterm labor, an increase in ILC2s and ILC3s was observed in the decidua basalis and decidua parietalis, respectively. These findings provide evidence demonstrating a role for ILCs at the maternal-fetal interface during the pathological process of preterm labor.