Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23

Lili Chen, Valentina Strohmeier, Zhengxiang He, Madhura Deshpande, Jovani Catalan-Dibene, Scott K. Durum, Thomas M. Moran, Thomas Kraus, Huabao Xiong, Jeremiah J. Faith, Chhinder Sodhi, David Hackam, Sergio A. Lira, Glaucia C. Furtado

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number4517
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

interleukins
Interleukin-23
mice
Infant, Newborn, Diseases
enzymes
effectors
pancreas
Food
Necrotizing Enterocolitis
secretions
phenotype
Acinar Cells
carbohydrates
nutrients
Myeloid Cells
Enzymes
Ablation
cells
Keratinocytes
food

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Chen, L., Strohmeier, V., He, Z., Deshpande, M., Catalan-Dibene, J., Durum, S. K., ... Furtado, G. C. (2019). Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23. Nature communications, 10(1), [4517]. https://doi.org/10.1038/s41467-019-12540-8

Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23. / Chen, Lili; Strohmeier, Valentina; He, Zhengxiang; Deshpande, Madhura; Catalan-Dibene, Jovani; Durum, Scott K.; Moran, Thomas M.; Kraus, Thomas; Xiong, Huabao; Faith, Jeremiah J.; Sodhi, Chhinder; Hackam, David; Lira, Sergio A.; Furtado, Glaucia C.

In: Nature communications, Vol. 10, No. 1, 4517, 01.12.2019.

Research output: Contribution to journalArticle

Chen, L, Strohmeier, V, He, Z, Deshpande, M, Catalan-Dibene, J, Durum, SK, Moran, TM, Kraus, T, Xiong, H, Faith, JJ, Sodhi, C, Hackam, D, Lira, SA & Furtado, GC 2019, 'Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23', Nature communications, vol. 10, no. 1, 4517. https://doi.org/10.1038/s41467-019-12540-8
Chen L, Strohmeier V, He Z, Deshpande M, Catalan-Dibene J, Durum SK et al. Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23. Nature communications. 2019 Dec 1;10(1). 4517. https://doi.org/10.1038/s41467-019-12540-8
Chen, Lili ; Strohmeier, Valentina ; He, Zhengxiang ; Deshpande, Madhura ; Catalan-Dibene, Jovani ; Durum, Scott K. ; Moran, Thomas M. ; Kraus, Thomas ; Xiong, Huabao ; Faith, Jeremiah J. ; Sodhi, Chhinder ; Hackam, David ; Lira, Sergio A. ; Furtado, Glaucia C. / Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23. In: Nature communications. 2019 ; Vol. 10, No. 1.
@article{bdac27f7019f413bbd77b47d30383909,
title = "Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23",
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.",
author = "Lili Chen and Valentina Strohmeier and Zhengxiang He and Madhura Deshpande and Jovani Catalan-Dibene and Durum, {Scott K.} and Moran, {Thomas M.} and Thomas Kraus and Huabao Xiong and Faith, {Jeremiah J.} and Chhinder Sodhi and David Hackam and Lira, {Sergio A.} and Furtado, {Glaucia C.}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-12540-8",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Interleukin 22 disrupts pancreatic function in newborn mice expressing IL-23

AU - Chen, Lili

AU - Strohmeier, Valentina

AU - He, Zhengxiang

AU - Deshpande, Madhura

AU - Catalan-Dibene, Jovani

AU - Durum, Scott K.

AU - Moran, Thomas M.

AU - Kraus, Thomas

AU - Xiong, Huabao

AU - Faith, Jeremiah J.

AU - Sodhi, Chhinder

AU - Hackam, David

AU - Lira, Sergio A.

AU - Furtado, Glaucia C.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85072909900&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072909900&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-12540-8

DO - 10.1038/s41467-019-12540-8

M3 - Article

C2 - 31586069

AN - SCOPUS:85072909900

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4517

ER -