Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque

Pietro Presicce, Monica Cappelletti, Marco Morselli, Feiyang Ma, Paranthaman Senthamaraikannan, Giulia Protti, Brian B. Nadel, Laila Aryan, Mansoureh Eghbali, Lukasz Salwinski, Neema Pithia, Emily De Franco, Lisa A. Miller, Matteo Pellegrini, Alan H. Jobe, Claire A. Chougnet, Suhas G. Kallapur

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.

Original languageEnglish
Article number108118
JournaliScience
Volume26
Issue number11
DOIs
StatePublished - Nov 17 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • Bioinformatics
  • Immunology
  • Omics

ASJC Scopus subject areas

  • General

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