Year: 2025
Type: article
Abstract: Neonatal necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease of premature infants, characterized by immune dysregulation and compromised intestinal barrier integrity. Interleukin-27 receptor α (IL-27Ra), a critical component of the JAK-STAT signaling pathway, exhibits dual pro- and anti-inflammatory roles in various inflammatory conditions. However, its role in NEC pathogenesis remains unclear. To elucidate the functional role of IL-27Ra in NEC development and assess its potential as a therapeutic target. A multi-tiered approach was employed, including integrative analysis of clinical NEC specimens by single-cell and bulk RNA sequencing, and a neonatal mouse NEC model. NEC was induced in mice via hyperosmolar formula feeding combined with LPS gavage, intermittent hypoxia, and cold stress. Additional experiments included immunofluorescence staining for IL-27Ra, cytokine profiling (ELISA, quantitative real-time PCR (qPCR)), use of IL-27Ra knockout (IL-27Ra-/-) mice, and histopathological scoring of intestinal injury. In NEC patient intestinal tissues, IL-27Ra expression was significantly upregulated in immune cells, with expression levels positively correlating with pro-inflammatory mediators (e.g., IL-6) and inversely correlating with barrier-associated proteins (e.g., TJP1). In the neonatal mouse NEC model, genetic ablation of IL-27Ra (IL-27Ra-/-) led to reduced histopathology scores, decreased IL-6 production (ELISA and qPCR), and restored tight junction protein expression (TJP1, OCLN). IL-27Ra promotes NEC by amplifying intestinal inflammation and damaging the mucosal barrier. Thus, IL-27Ra is identified as a promising therapeutic target. Pharmacological blockade of IL-27Ra signaling may provide a dual benefit in NEC—mitigating excessive inflammation while restoring barrier integrity. These findings are primarily derived from NEC mouse models and await clinical validation.
Source: Scientific Reports
Authors: Yuling Yang, Yingyan Liu, Limei Zhong, Chun Yan, Xin Zhong, Chaoting Lan, Sitao Li, Yufeng Liu
Institutions: Guangzhou First People's Hospital, South China University of Technology, Guangdong Provincial People's Hospital, Guangzhou Women and Children Medical Center, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Medical University, Sun Yat-sen University, Sixth Affiliated Hospital of Sun Yat-sen University
Language: English
Topic: Infant Nutrition and Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W4416784051