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

doi:10.1016/j.isci.2023.108118

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

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

6 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 language	English
Article number	108118
Journal	iScience
Volume	26
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2023.108118
State	Published - Nov 17 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Funding

This study was supported by R01 HD98389 (SK) and by U01 ES029234 (CC). We thank Sarah Davis, Jennifer Kendrick, Sarah Lockwood, Anne Gibbons, Paul-Michael Sosa, Ma Zhong-Min, and Marie Jose-Lemoy research personnel at the CNPRC, UC Davis, for help with the animals. We also thank the Technology Center for Genomics & Bioinformatics (TCGB) at UCLA for scRNA library construction and sequencing; the Broad Stem Cell Research Center (BSCRC) at UCLA for bulk RNA-seq; the Institute for Quantitative & Computational Biosciences – Collaboratory for RNA-seq analysis; and the Immune Assessment Core (IAC) for ELISA multiplex. The Graphical Abstract was created with BioRender.com (https://BioRender.com). P.P. M.C. M.M. and P.S. participated in data generation. P.P. M.C. M.M. B.B.N. F.M. G.P. L.A. M.E. N.P. L.S. M.P. E.D.F. A.H.J. C.A.C. and S.G.K. participated in analysis and interpretation of data. A.H.J. C.A.C. and S.G.K. participated in the conception and design of the study and obtained the funding. P.P. and S.G.K. wrote the manuscript. All authors have reviewed the manuscript and approve the final version. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.

Funders	Funder number
Immune Assessment Core
Institute for Quantitative & Computational Biosciences
Marie Jose-Lemoy
Technology Center for Genomics & Bioinformatics
University of California, Los Angeles
University of California Davis
California National Primate Research Center
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles

Keywords

Bioinformatics
Immunology
Omics

ASJC Scopus subject areas

General

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10.1016/j.isci.2023.108118

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Presicce, P., Cappelletti, M., Morselli, M., Ma, F., Senthamaraikannan, P., Protti, G., Nadel, B. B., Aryan, L., Eghbali, M., Salwinski, L., Pithia, N., De Franco, E., Miller, L. A., Pellegrini, M., Jobe, A. H., Chougnet, C. A., & Kallapur, S. G. (2023). Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque. iScience, 26(11), Article 108118. https://doi.org/10.1016/j.isci.2023.108118

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title = "Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque",

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.",

keywords = "Bioinformatics, Immunology, Omics",

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

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = nov,

day = "17",

doi = "10.1016/j.isci.2023.108118",

language = "English",

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Presicce, P, Cappelletti, M, Morselli, M, Ma, F, Senthamaraikannan, P, Protti, G, Nadel, BB, Aryan, L, Eghbali, M, Salwinski, L, Pithia, N, De Franco, E, Miller, LA, Pellegrini, M, Jobe, AH, Chougnet, CA & Kallapur, SG 2023, 'Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque', iScience, vol. 26, no. 11, 108118. https://doi.org/10.1016/j.isci.2023.108118

TY - JOUR

T1 - Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque

AU - Presicce, Pietro

AU - Cappelletti, Monica

AU - Morselli, Marco

AU - Ma, Feiyang

AU - Senthamaraikannan, Paranthaman

AU - Protti, Giulia

AU - Nadel, Brian B.

AU - Aryan, Laila

AU - Eghbali, Mansoureh

AU - Salwinski, Lukasz

AU - Pithia, Neema

AU - De Franco, Emily

AU - Miller, Lisa A.

AU - Pellegrini, Matteo

AU - Jobe, Alan H.

AU - Chougnet, Claire A.

AU - Kallapur, Suhas G.

PY - 2023/11/17

Y1 - 2023/11/17

N2 - 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.

AB - 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.

KW - Bioinformatics

KW - Immunology

KW - Omics

UR - https://www.scopus.com/pages/publications/85175456960

UR - https://www.scopus.com/inward/citedby.url?scp=85175456960&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2023.108118

DO - 10.1016/j.isci.2023.108118

M3 - Article

AN - SCOPUS:85175456960

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 11

M1 - 108118

ER -

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

Abstract

Bibliographical note

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Keywords

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