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 P. Sodhi, David J. Hackam, Sergio A. Lira () and Glaucia C. Furtado ()
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Lili Chen: Icahn School of Medicine at Mount Sinai
Valentina Strohmeier: Icahn School of Medicine at Mount Sinai
Zhengxiang He: Icahn School of Medicine at Mount Sinai
Madhura Deshpande: Icahn School of Medicine at Mount Sinai
Jovani Catalan-Dibene: Icahn School of Medicine at Mount Sinai
Scott K. Durum: National Cancer Institute
Thomas M. Moran: Icahn School of Medicine at Mount Sinai
Thomas Kraus: Icahn School of Medicine at Mount Sinai
Huabao Xiong: Icahn School of Medicine at Mount Sinai
Jeremiah J. Faith: Icahn School of Medicine at Mount Sinai
Chhinder P. Sodhi: Johns Hopkins Hospital
David J. Hackam: Johns Hopkins Hospital
Sergio A. Lira: Icahn School of Medicine at Mount Sinai
Glaucia C. Furtado: Icahn School of Medicine at Mount Sinai

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12540-8

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