Characterization of murine amniotic fluid B cells in normal pregnancy and in preterm birth

Bommer, I.; Juriol, Lorena; Muzzio, Damián Oscar; Valeff, Natalin Jimena; Ehrhardt, Jens; Matzner, Franziska; Ziegler, Katharina; Malinowsky, Kristin; Ventimiglia, Maria; Zygmunt, Marek; Jensen, Federico

doi:10.1530/rep-19-0150

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…Bommer at al. reported on an increase of B cells in the amniotic fluid following LPS injection and suggested that B cells may serve as an immunological protective barrier against PTB [45]. Earlier studies found that administration of high-dose LPS i.p.…”

Section: Discussionmentioning

confidence: 99%

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

Uehre,

Tchaikovski,

Ignatov

et al. 2023

IJMS

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The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19−/−, BMyD88−/− and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19−/−, BMyD88−/− and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB.

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Section: Discussionmentioning

confidence: 99%

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

Uehre,

Tchaikovski,

Ignatov

et al. 2023

IJMS

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“…The AF, a crucial component of the intrauterine environment, is known to harbor a diverse population of immune cells that play a pivotal role in maintaining maternal-fetal tolerance and protecting against intrauterine infections [70]. Among the various immune cells present in the AF, macrophages, neutrophils, T cells, B cells, and natural killer cells have been identified as key players in orchestrating immune responses within the gestational compartment [71][72][73]. However, we only identified macrophage in cultured AFCs from fetuses with NTDs.…”

Section: Discussionmentioning

confidence: 99%

Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis

Wang,

Ji,

Dong

et al. 2024

J Transl Med

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Background Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model. Methods Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model. Results Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs. Conclusions Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics.

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“…67,68 Recent studies have identified the critical role of B cells in birth timing and preterm birth in animals and humans. [69][70][71] In mice, the expression level of EBF1 at the mRNA level is downregulated in splenic B cells during normal pregnancies. 72 Low EBF1 mRNA has been associated with an increased risk of sPTB in humans due to altered maternal-fetal immune and cell cycle/apoptosis pathways.…”

Section: Genome-wide Association Studiesmentioning

confidence: 99%

“…EBF1 is essential for B cell development and control of blood pressure 67,68 . Recent studies have identified the critical role of B cells in birth timing and preterm birth in animals and humans 69–71 . In mice, the expression level of EBF1 at the mRNA level is downregulated in splenic B cells during normal pregnancies 72 .…”

Section: Family‐based and Epidemiological Evidence For Preterm Birthmentioning

confidence: 99%

Genetics, epigenetics, and transcriptomics of preterm birth

Jain

Monangi

Zhang

et al. 2022

American J Rep Immunol

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Preterm birth contributes significantly to neonatal mortality and morbidity. Despite its global significance, there has only been limited progress in preventing preterm birth. Spontaneous preterm birth (sPTB) results from a wide variety of pathological processes. Although many non‐genetic risk factors influence the timing of gestation and labor, compelling evidence supports the role of substantial genetic and epigenetic influences and their interactions with the environment contributing to sPTB. To investigate a common and complex disease such as sPTB, various approaches such as genome‐wide association studies, whole‐exome sequencing, transcriptomics, and integrative approaches combining these with other ‘omics studies have been used. However, many of these studies were typically small or focused on a single ethnicity or geographic region with limited data, particularly in populations at high risk for sPTB, or lacked a robust replication. These studies found many genes involved in the inflammation and immunity‐related pathways that may affect sPTB. Recent studies also suggest the role of epigenetic modifications of gene expression by the environmental signals as a potential contributor to the risk of sPTB. Future genetic studies of sPTB should continue to consider the contributions of both maternal and fetal genomes as well as their interaction with the environment.

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Characterization of murine amniotic fluid B cells in normal pregnancy and in preterm birth

Cited by 6 publications

References 28 publications

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection

Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis

Genetics, epigenetics, and transcriptomics of preterm birth

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