Murine intestinal epithelial cells and lymphocytes undergo contrasting inflammatory shifts during gastrointestinal development.

BACKGROUND: The gastrointestinal tract is particularly vulnerable to strong inflammatory responses during early development as seen in preterm infants with necrotizing enterocolitis (NEC). Intestinal maturation plays a crucial role in the pathogenesis of this condition. METHODS: Given the limited availability of human samples across different stages of gastrointestinal maturation, this study utilised a murine model that closely mirrors the fetal, preterm, term, and adult stages of human development. We investigated baseline and lipopolysaccharide (LPS)-induced inflammatory responses in isolated primary intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs). RESULTS: IECs displayed greater sensitivity to LPS at early developmental stages, with reduced responsiveness as maturation progressed. In contrast, IELs exhibited inflammatory reactivity only at later stages. Regulation of phosphorylated p65 in both cell populations highlighted the role of the TLR-4/NFĸB pathway in these maturation-dependent responses. CONCLUSION: A proinflammatory shift in key epithelial cell populations was observed, reflecting the development of the gastrointestinal system. These findings enhance the understanding of NEC pathogenesis and provide translational insights into intestinal inflammatory responses during maturation. IMPACT: Intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) exhibit contrasting inflammatory responses during gastrointestinal maturation, with IECs being more reactive in early stages and IELs becoming reactive later. This study provides a detailed correlation between human and murine intestinal development, offering insights into maturation-dependent inflammatory mechanisms and the role of the TLR-4/NFĸB pathway. Our findings enhance understanding of gastrointestinal maturation and its role in inflammatory diseases like necrotizing enterocolitis (NEC).