IL-27Ra promotes the progression of neonatal necrotizing enterocolitis

Yuling Yang ¹, Yingyan Liu ¹, Limei Zhong ²

⁰Center for Medical Research On Innovation and Translation, Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, 510000, Guangdong, China.

Scientific Reports +

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November 29, 2025

View abstract on PubMed

Summary

Interleukin-27 receptor alpha (IL-27Ra) exacerbates necrotizing enterocolitis (NEC) in premature infants by increasing inflammation and damaging the gut barrier. Blocking IL-27Ra may offer a dual therapeutic benefit for NEC.

Area Of Science

Gastroenterology
Immunology
Neonatal Medicine

Background

Neonatal necrotizing enterocolitis (NEC) is a severe condition in premature infants, marked by immune imbalance and intestinal barrier defects.
The role of Interleukin-27 receptor alpha (IL-27Ra) in NEC pathogenesis is not well understood, despite its known dual roles in inflammation.

Purpose Of The Study

To investigate the function of IL-27Ra in the development of NEC.
To evaluate IL-27Ra as a potential therapeutic target for NEC.

Main Methods

Integrative analysis of human NEC tissues using single-cell and bulk RNA sequencing.
Induction of NEC in a neonatal mouse model with hyperosmolar feeding, LPS, hypoxia, and cold stress.
Assessment using immunofluorescence, cytokine profiling (ELISA, qPCR), IL-27Ra knockout mice, and histopathology.

Main Results

IL-27Ra was upregulated in immune cells of NEC patient tissues, correlating with pro-inflammatory cytokines (IL-6) and reduced barrier proteins (TJP1).
IL-27Ra knockout mice showed reduced NEC severity, lower IL-6 levels, and improved tight junction protein expression.
IL-27Ra was found to promote NEC by enhancing intestinal inflammation and compromising the mucosal barrier.

Conclusions

IL-27Ra plays a significant role in promoting NEC pathogenesis.
IL-27Ra represents a promising therapeutic target for NEC.
Targeting IL-27Ra signaling could simultaneously reduce inflammation and restore intestinal barrier function in NEC.

Keywords:

IL-27Ra Intestinal barrier Intestinal inflammation Neonatal immunity Neonatal necrotizing enterocolitis

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