Centers and Institutes
Published May 16, 2023 | Version v1
Journal article Open

Single cell profiling at the maternal–fetal interface reveals a deficiency of PD-L1+ non-immune cells in human spontaneous preterm labor

Creators

  • 1. University of Chicago
  • 2. Mayo Clinic
  • 3. Rutgers University
  • 4. Duke University
  • 5. Northwestern University

Description

The mechanisms that underlie the timing of labor in humans are largely unknown. In most pregnancies, labor is initiated at term (≥ 37 weeks gestation), but in a signifiicant number of women spontaneous labor occurs preterm and is associated with increased perinatal mortality and morbidity. The objective of this study was to characterize the cells at the maternal–fetal interface (MFI) in term and preterm pregnancies in both the laboring and non-laboring state in Black women, who have among the highest preterm birth rates in the U.S. Using mass cytometry to obtain high-dimensional single-cell resolution, we identified 31 cell populations at the MFI, including 25 immune cell types and six non-immune cell types. Among the immune cells, maternal PD1+ CD8 T cell subsets were less abundant in term laboring compared to term non-laboring women. Among the non-immune cells, PD-L1+ maternal (stromal) and fetal (extravillous trophoblast) cells were less abundant in preterm laboring compared to term laboring women. Consistent with these observations, the expression of CD274, the gene encoding PD-L1, was significantly depressed and less responsive to fetal signaling molecules in cultured mesenchymal stromal cells from the decidua of preterm compared to term women. Overall, these results suggest that the PD1/PD-L1 pathway at the MFI may perturb the delicate balance between immune tolerance and rejection and contribute to the onset of spontaneous preterm labor.

Data availability

All CyTOF data generated or analyzed during this study are available at https://www.immport.org/shared/study/SDY2075. All software and algorithms used to process data are shown in Supplementary Table 9.

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Additional details

Identifiers

DOI
10.1038/s41598-023-35051-5
Other
oai:uchicago.tind.io:6006

Funding

March of Dimes
Chicago-Northwestern-Duke Prematurity Research Center grant

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics, Obstetrics and Gynecology
Center(s) or Institute(s)
Center for Research Informatics