Alterations in Resident Immune Cells in Prenatal Trisomy 21 Lungs

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.