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 language | English (US) |
|---|---|
| Article number | 4517 |
| Journal | Nature communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2019 |
Fingerprint
ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
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 journal › Article
}
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 -