title: Eosinophils secrete IL-4 to facilitate liver regeneration.
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.
authors.affiliation: Department of Genetics and Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Y P Sharon
authors.initials: YP
authors.lastname: Goh
authors.forename: Neil C
authors.initials: NC
authors.lastname: Henderson
authors.forename: Jose E
authors.initials: JE
authors.lastname: Heredia
authors.forename: Alex
authors.initials: A
authors.lastname: Red Eagle
authors.forename: Justin I
authors.initials: JI
authors.lastname: Odegaard
authors.forename: Nadja
authors.initials: N
authors.lastname: Lehwald
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Nguyen
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
authors.forename: Lata
authors.initials: L
authors.lastname: Mukundan
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
authors.forename: Ajay
authors.initials: A
authors.lastname: Chawla
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D004804:Eosinophils / Q000378:metabolism*; D020869:Gene Expression Profiling; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D015151:Immunoblotting; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000502:physiology* / Q000601:surgery; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D053662:Interleukin-4 Receptor alpha Subunit; D015847:Interleukin-4
keywords: inflammation; parasites; tissue injury and repair; type 2 immunity