Unique metabolism and protein expression signature in human decidual NK cells

Ping Wang; Tingting Liang; Heqin Zhan; Mingming Zhu; Mingming Wu; Lili Qian; Ying Zhou; Fang Ni

doi:10.3389/fimmu.2023.1136652

Unique metabolism and protein expression signature in human decidual NK cells

Front Immunol. 2023 Mar 3:14:1136652. doi: 10.3389/fimmu.2023.1136652. eCollection 2023.

Authors

Ping Wang^{1

2}, Tingting Liang^{1

2}, Heqin Zhan³, Mingming Zhu^{1

2}, Mingming Wu^{1

2}, Lili Qian⁴, Ying Zhou⁴, Fang Ni^{1

2}

Affiliations

¹ Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China (USTC), The Chinese Academy of Science (CAS) Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
² Institute of Immunology, University of Science and Technology of China, Hefei, China.
³ Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
⁴ Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Abstract

Human decidual natural killer (dNK) cells are a unique type of tissue-resident NK cells at the maternal-fetal interface. dNK cells are likely to have pivotal roles during pregnancy, including in maternal-fetal immune tolerance, trophoblast invasion, and fetal development. However, detailed insights into these cells are still lacking. In this study, we performed metabolomic and proteomic analyses on human NK cells derived from decidua and peripheral blood. We found that 77 metabolites were significantly changed in dNK cells. Notably, compared to peripheral blood NK (pNK) cells, 29 metabolites involved in glycerophospholipid and glutathione metabolism were significantly decreased in dNK cells. Moreover, we found that 394 proteins were differentially expressed in dNK cells. Pathway analyses and network enrichment analyses identified 110 differentially expressed proteins involved in focal adhesion, cytoskeleton remodeling, oxidoreductase activity, and fatty acid metabolism in dNK cells. The integrated proteomic and metabolomic analyses revealed significant downregulation in glutathione metabolism in dNK cells compared to pNK cells. Our data indicate that human dNK cells have unique metabolism and protein-expression features, likely regulating their function in pregnancy and immunity.

Keywords: decidua; glutathione; glycerophospholipid; metabolomics; natural killer cell; proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Down-Regulation
Female
Glutathione / metabolism
Humans
Killer Cells, Natural*
Pregnancy
Proteomics*

Substances

Glutathione

Grants and funding

This work was supported by the National Key Research and Development Program of China (No. 2019YFA0801800), the Natural Science Foundation of China (No. 32070916), and Anhui Natural Science Foundation for Distinguished Young Scholars (No. 2108085J38).