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Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface
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Alterations in Resident Immune Cells in Prenatal Trisomy 21 Lungs

Andrew Frauenpreis1, Soumyaroop Bhattacharya2, Randa Belgacemi1

  • 1Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

Cells
|December 10, 2025
PubMed

Insights

Children with Down syndrome (DS), also known as Trisomy 21 (T21), show reduced B cells in prenatal lungs. This may explain their higher risk for respiratory tract infections (RTIs).

Area of Science:

  • Immunology
  • Genetics
  • Developmental Biology

Background:

  • Children with Down syndrome (DS) experience high rates of respiratory tract infections (RTIs), leading to frequent hospitalizations.
  • This increased susceptibility is linked to anatomical differences in airways and immune system dysfunctions.
  • Understanding prenatal immune development in DS is crucial for explaining early-life vulnerability.

Purpose of the Study:

  • To characterize the immune cell landscape in prenatal lungs of individuals with Trisomy 21 (T21).
  • To identify potential immune system alterations contributing to the heightened risk of RTIs in DS.
  • To investigate changes in B cell populations and their maturation markers in utero.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) was employed to profile immune cells from prenatal T21 (n=5) and non-T21 (n=4) lungs.
  • Spatial phenotypes were analyzed using fluorescent in situ hybridization and immunofluorescent staining.
  • Gene expression and protein levels of B cell markers (e.g., CD20, CD38) were assessed via qRT-PCR and immunofluorescence.

Main Results:

  • A significant decrease in the percentage of B cells was observed in T21 prenatal lungs compared to controls (FDR = 0.0037).
  • Key B cell maturation markers showed significantly reduced expression at both gene (qRT-PCR) and protein (CD20, CD38) levels in T21 lungs.
  • Differential gene expression analysis identified 84 differentially expressed genes across 14 immune cell clusters.

Conclusions:

  • Prenatal lung immune system development is altered in Trisomy 21, specifically impacting the B cell compartment.
  • Reduced B cell populations and impaired maturation in utero may underlie the increased susceptibility to respiratory infections in infants with Down syndrome.
  • These findings highlight the importance of early immune monitoring and potential therapeutic interventions for respiratory health in DS.

Keywords:
B cellsDown syndrometranscriptomics

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