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Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9914-9. doi: 10.1073/pnas.1304046110. Epub 2013 May 28.

Eosinophils secrete IL-4 to facilitate liver regeneration.

Author information

1
Department of Genetics and Pathology, Stanford University, Stanford, CA 94305, USA.

Abstract

The liver is a central organ for the synthesis and storage of nutrients, production of serum proteins and hormones, and breakdown of toxins and metabolites. Because the liver is susceptible to toxin- or pathogen-mediated injury, it maintains a remarkable capacity to regenerate by compensatory growth. Specifically, in response to injury, quiescent hepatocytes enter the cell cycle and undergo DNA replication to promote liver regrowth. Despite the elucidation of a number of regenerative factors, the mechanisms by which liver injury triggers hepatocyte proliferation are incompletely understood. We demonstrate here that eosinophils stimulate liver regeneration after partial hepatectomy and toxin-mediated injury. Liver injury results in rapid recruitment of eosinophils, which secrete IL-4 to promote the proliferation of quiescent hepatocytes. Surprisingly, signaling via the IL-4Rα in macrophages, which have been implicated in tissue repair, is dispensable for hepatocyte proliferation and liver regrowth after injury. Instead, IL-4 exerts its proliferative actions via IL-4Rα in hepatocytes. Our findings thus provide a unique mechanism by which eosinophil-derived IL-4 stimulates hepatocyte proliferation in regenerating liver.

KEYWORDS:

inflammation; parasites; tissue injury and repair; type 2 immunity

PMID:
23716700
PMCID:
PMC3683773
DOI:
10.1073/pnas.1304046110
[Indexed for MEDLINE]
Free PMC Article
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