Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23. Academic Article uri icon

Overview

abstract

  • Neonatal inflammatory diseases are associated with severe morbidity, but the inflammatory factors underlying them and their potential effector mechanisms are poorly defined. Here we show that necrotizing enterocolitis in neonate mice is accompanied by elevation of IL-23 and IL-22 and decreased production of pancreatic enzymes. These phenotypes are mirrored in neonate mice overexpressing IL-23 in CX3CR1+ myeloid cells or in keratinocytes. The mice fail to grow and die prematurely, displaying systemic inflammation, nutrient malabsorption and decreased expression of intestinal and pancreatic genes mediating digestion and absorption of carbohydrates, proteins, and lipids. Germ-free environment improves, and genetic ablation of IL-22 restores normal growth in mice overexpressing IL-23. Mechanistically, IL-22 acts directly at the level of pancreatic acinar cells to decrease expression of the pancreas associated transcription factor 1a (PTF1a). These results show that augmented production of IL-23 and IL-22 in early life has a negative impact on pancreatic enzyme secretion and food absorption.

publication date

  • October 4, 2019

Research

keywords

  • Enterocolitis, Necrotizing
  • Interleukin-23
  • Interleukins
  • Pancreas
  • Transcription Factors

Identity

PubMed Central ID

  • PMC6778080

Scopus Document Identifier

  • 85072909900

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-12540-8

PubMed ID

  • 31586069

Additional Document Info

volume

  • 10

issue

  • 1