Eosinophils secrete IL-4 to facilitate liver regeneration

Y P Sharon Goh, Neil C Henderson, Jose E Heredia, Alex Red Eagle, Justin I Odegaard, Nadja Lehwald, Khoa D Nguyen, Dean Sheppard, Lata Mukundan, Richard M Locksley, Ajay Chawla

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)9914-9919
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number24
Publication statusPublished - 11 Jun 2013

Keywords / Materials (for Non-textual outputs)

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


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