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Endoplasmic reticulum stress, unfolded protein response and altered T cell differentiation in necrotizing

Peng Lu1, Marie-Chantal Struijs, Jiaping Mei

  • 1Division of Neonatology, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, the Netherlands ; Department of Pediatrics, Emma Children's Hospital - AMC, Amsterdam, The Netherlands.

Plos One
|November 7, 2013
PubMed

Insights

Necrotizing enterocolitis (NEC) involves endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), particularly XBP1 splicing. This is linked to increased inflammation, altered T cell responses, and severe intestinal injury in infants.

Area of Science:

  • Gastroenterology
  • Pediatric Surgery
  • Molecular Biology

Background:

  • Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are implicated in chronic intestinal inflammation.
  • Necrotizing enterocolitis (NEC) is a critical gastrointestinal emergency in preterm infants, characterized by acute intestinal inflammation and necrosis.

Purpose of the Study:

  • To investigate the specific role and molecular mechanisms of ER stress and UPR activation in NEC patients.

Main Methods:

  • Analysis of ileal tissues from NEC and control infants.
  • Detection of XBP1 splicing via PCR.
  • Quantification of gene expression using qPCR and Western blot.

Main Results:

  • XBP1 splicing was detected in a subset of acute NEC (A-NEC) patients, but not in reanastomosed NEC (R-NEC) patients.
  • A-NEC patients with XBP1 splicing (A-NEC-XBP1s) exhibited increased expression of GRP78, CHOP, IL6, and IL8.
  • A-NEC-XBP1s patients showed altered T cell differentiation (decreased RORC, IL17A, FOXP3) and more severe clinical outcomes.

Conclusions:

  • XBP1 splicing, ER stress, and UPR activation in NEC are associated with elevated IL6 and IL8 levels.
  • These molecular pathways correlate with disrupted T cell differentiation and significant epithelial injury in NEC.
  • Findings suggest XBP1 splicing as a potential biomarker for NEC severity and outcome.
Abstract

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