Multimodal profiling of term human decidua demonstrates immune adaptations with pregravid obesity

Suhas Sureshchandra; Brianna M. Doratt; Heather True; Norma Mendoza; Monica Rincon; Nicole E. Marshall; Ilhem Messaoudi

doi:10.1016/j.celrep.2023.112769

Multimodal profiling of term human decidua demonstrates immune adaptations with pregravid obesity

Suhas Sureshchandra
, Brianna M. Doratt
, Heather True
, Norma Mendoza
, Monica Rincon
, Nicole E. Marshall
, Ilhem Messaoudi

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

18 Scopus citations

Abstract

Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to bacterial ligands is reduced with pregravid obesity, suggestive of skewing toward immunoregulation as a possible mechanism to safeguard the fetus against excessive maternal inflammation. These findings are a resource for future studies investigating pathological conditions that compromise fetal health and reproductive success.

Original language	English
Article number	112769
Journal	Cell Reports
Volume	42
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2023.112769
State	Published - Jul 25 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Funding

We are grateful to all participants in this study. We thank the MFM Research Unit at Oregon Health and Science University for sample collection and Allen Jankeel, Michael Z. Zulu, Gouri Ajith, Isaac Cinco, and Hannah Debray at University of California, Irvine (UCI) for assistance with tissue processing. We thank Dr. Jennifer Atwood at the UCI Institute for Immunology Flow Cytometry Core for assistance with FACS sorting, imaging flow cytometry and Dr. Melanie Oakes at the UCI Genomics Research and Technology Hub (GRT Hub) for assistance with 10x library preparation and sequencing. This study was supported by grants from the National Institutes of Health 1K23HD06952 (N.E.M.), 1R01AI145910 (I.M.), R03AI11280 (I.M.), and 1R01AI142841 (I.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Conceptualization, S.S. N.E.M. and I.M.; methodology, S.S. N.E.M. and I.M.; investigation, S.S. B.D. H.T. and N.M; writing, S.S. H.T. and I.M.; funding acquisition, N.E.M. and I.M.; resources, M.R. N.E.M. All authors have read and approved the final draft of the manuscript. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. We are grateful to all participants in this study. We thank the MFM Research Unit at Oregon Health and Science University for sample collection and Allen Jankeel, Michael Z. Zulu, Gouri Ajith, Isaac Cinco, and Hannah Debray at University of California, Irvine (UCI) for assistance with tissue processing. We thank Dr. Jennifer Atwood at the UCI Institute for Immunology Flow Cytometry Core for assistance with FACS sorting, imaging flow cytometry and Dr. Melanie Oakes at the UCI Genomics Research and Technology Hub (GRT Hub) for assistance with 10x library preparation and sequencing. This study was supported by grants from the National Institutes of Health 1K23HD06952 (N.E.M.), 1R01AI145910 (I.M.), R03AI11280 (I.M.), and 1R01AI142841 (I.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH .

Funders	Funder number
UCI Genomics Research and Technology Hub
National Institutes of Health (NIH)	1K23HD06952, 1R01AI142841, 1R01AI145910, R03AI11280
University of California Irvine
Urban Child Institute

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CP: Immunology
TCR
decidua
human
macrophages
maternal-fetal interface
obesity

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2023.112769

Cite this

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title = "Multimodal profiling of term human decidua demonstrates immune adaptations with pregravid obesity",

abstract = "Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to bacterial ligands is reduced with pregravid obesity, suggestive of skewing toward immunoregulation as a possible mechanism to safeguard the fetus against excessive maternal inflammation. These findings are a resource for future studies investigating pathological conditions that compromise fetal health and reproductive success.",

keywords = "CP: Immunology, TCR, decidua, human, macrophages, maternal-fetal interface, obesity",

author = "Suhas Sureshchandra and Doratt, \{Brianna M.\} and Heather True and Norma Mendoza and Monica Rincon and Marshall, \{Nicole E.\} and Ilhem Messaoudi",

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doi = "10.1016/j.celrep.2023.112769",

language = "English",

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AU - Sureshchandra, Suhas

AU - Doratt, Brianna M.

AU - True, Heather

AU - Mendoza, Norma

AU - Rincon, Monica

AU - Marshall, Nicole E.

AU - Messaoudi, Ilhem

PY - 2023/7/25

Y1 - 2023/7/25

N2 - Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to bacterial ligands is reduced with pregravid obesity, suggestive of skewing toward immunoregulation as a possible mechanism to safeguard the fetus against excessive maternal inflammation. These findings are a resource for future studies investigating pathological conditions that compromise fetal health and reproductive success.

AB - Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to bacterial ligands is reduced with pregravid obesity, suggestive of skewing toward immunoregulation as a possible mechanism to safeguard the fetus against excessive maternal inflammation. These findings are a resource for future studies investigating pathological conditions that compromise fetal health and reproductive success.

KW - CP: Immunology

KW - TCR

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Multimodal profiling of term human decidua demonstrates immune adaptations with pregravid obesity

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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Cite this