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.type 2 immunity | tissue injury and repair | inflammation | parasites

Immunity to gastrointestinal nematode infections

“…Thus, despite being redundant for the expulsion of most nematodes, eosinophils might be important for wound healing and tissue regeneration in which they have been implicated in nonmucosal tissues. [194][195][196] Eosinophils have also been shown to promote the survival of long-lived plasma cells in the bone marrow 197 as well as the generation of IgA-secreting plasma cells in the gastrointestinal tract 179,198 (at least in the small intestine 199 ) via the production of IL-1b, suggesting that they might affect secondary challenge infections where antibodies presumably play a larger role. Indeed, both IL-5 and eosinophildeficient mice harbor increased numbers of N. brasiliensis larvae after secondary infection, 89 with similar results during secondary T. spiralis infection.…”

IL-4 gene expression in adventitial layer (fibrous layer) of hepatic ovine and bovine hydatid cysts

“…In this context different studies have shown a potential role for eosinophils in tissue repair (Goh et al 2013;Heredia et al 2013;Rosenberg et al 2012). Also it has been shown that IL-4 secreted by eosinophils has been implicated in both wound repair and liver regeneration (Anthony et al 2007;Chen et al 2012;Gallagher et al 2007;Goh et al 2013;Murray and Wynn 2011;Palm et al 2012).…”

“…IL4 is secreted by eosinophils, so the presence of these cells in fibrous layer may be an indication of liver tissue damage (Goh et al 2013) or may be related to cellular immune response to the hydatid cyst. In this context different studies have shown a potential role for eosinophils in tissue repair (Goh et al 2013;Heredia et al 2013;Rosenberg et al 2012).…”

Macrophages – sensors and effectors coordinating skin damage and repair

“…Helminths are among the best characterized inducers of type 2 signals and subsequent M2-polarization [33]. Most recent findings report on the interesting observation that type 2 signals control skeletal muscle and liver regeneration [55,56]. In addition, preclinical studies and ongoing clinical trials suggest that controlled infection with helminths dampens inflammatory immune responses, thereby protecting the host from inflammation mediated tissue damage (Table 2).…”