Hif1α Deletion Limits Tissue Regeneration via Aberrant B Cell Accumulation in Experimental Pancreatitis

Publication date: 19 June 2018
Source:Cell Reports, Volume 23, Issue 12
Author(s): Kyoung Eun Lee, Michelle Spata, Richard Maduka, Robert H. Vonderheide, M. Celeste Simon
Pancreatitis is an inflammatory disease of the exocrine pancreas and ranks among the most common gastrointestinal disorders. Inflamed tissues frequently experience conditions of insufficient oxygen availability, or hypoxia. Here, we demonstrate that hypoxia and consequent stabilization of the hypoxia-inducible factor 1α (HIF1α) transcription factor occur in murine and human pancreatitis. Mice lacking pancreas-specific HIF1α expression display markedly impaired pancreatic regeneration following cerulein-induced pancreatitis, which is associated with excessive intrapancreatic B cell accumulation. Notably, B cell depletion in mice with established pancreatitis significantly enhances tissue regeneration. Our study reveals a crosstalk between pancreatic HIF1α expression and B cell trafficking that regulates tissue regeneration, and identifies plausible molecular targets for treating pancreatitis patients.

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Teaser

Lee et al. show that pancreas-specific HIF1α ablation impairs pancreatic regeneration following experimental pancreatitis, coincident with prominent increases in intrapancreatic B cells. B cell depletion in established pancreatitis accelerates tissue regeneration, indicating that HIF1α facilitates pancreatic regeneration by limiting intrapancreatic B cell accumulation.


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