Differences in immune cells and gene expression in human milk by parity on integrated scRNA sequencing

Clin Exp Pediatr. 2025 Jan 10. doi: 10.3345/cep.2024.01585. Online ahead of print.

Abstract

Background: Human breast milk (HBM) is an important source of tolerogenic immune mediators that influence the infant immune system. HBM-derived immune components are affected by various factors; however, few studies have examined the relationship between parity and immune cell profiles of HBM.

Purpose: This study aimed to clarify the effects of parity on HBM immune cell heterogeneity and gene expression by integrating and analyzing publicly available single-cell RNA sequencing datasets.

Results: The proportion of innate immune cells was significantly higher in the primiparous versus multiparous group, whereas the proportion of adaptive immune cells was significantly higher in the multiparous group (p = 0.021). The two immune clusters were re-annotated and classified into monocyte, T/B cell, and CD45 groups. The proportions of monocytes and T/B cells were higher in the primiparous and multiparous groups, respectively. In a gene set enrichment analysis of monocytes, genes with a direct role in the infant immune system and immune response-related genes were more highly expressed in the primiparous group.

Conclusion: Our results support the parity-dependent differences in gene expression between innate and adaptive immune cells.

Keywords: Human milk; Parity; single-cell RNA-seq.