Meteorin-like/Meteorin-β Is a Novel Immunoregulatory Cytokine Associated with Inflammation

Abstract

We have described a novel cytokine encoded by a gene called Meteorin-like (Metrnl). Metrnl is a small (~27kDa) secreted protein expressed by activated macrophages and barrier tissues (mucosa, skin). Metrnl production by bone marrow macrophages is induced by several cytokines including TNFα, IL-17α, IL-12 and IL-4 and inhibited by IFNγ and TGFβ. Metrnl expression in macrophages is also induced by lipopolysaccharide (LPS) and its levels in circulation are associated with inflammatory responses in vivo. Furthermore, Metrnl regulates the production of several cytokines and chemokines in macrophages. We have produced a Metrnl−/− mouse which is viable and shows normal development. However, it exhibits dysregulated cytokine production, alterations in IgG production, and is highly susceptible to LPS in a sepsis model. Furthermore, older Metrnl−/− mice develop inflammatory lesions, suggesting that Metrnl participates in the control of inflammatory responses. Taken together, these observations indicate that Metrnl encodes a novel immunoregulatory cytokine associated with inflammatory responses that we have designated Meteorin Beta.

Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism

“…Still, Stat3 signalling has been shown to promote macrophage differentiation into the M2/anti-inflammatory phenotype 22,23 and appears to be a mechanism for Metrnl to promote the anti-inflammatory/ regenerative potential of muscle regeneration. Moreover, Metrnl induces macrophage gene expression of both pro-(IL-6) and antiinflammatory (IGF-1/IL-10) genes 24 which could default to the antiinflammatory side of Stat3 signalling; this is observed during dual treatment of IL-10 and IL-6 (ref. 25 ).…”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…Meteorin-like (Metrnl) is a novel small (~27kDa) secreted adipocytokine that has a beneficial effect on glucose homeostasis and that also functions as a novel immunoregulatory cytokine associated with anti-inflammatory effects [ 307 , 308 , 309 ]. Metrnl has been proposed to connect adaptive responses to the regulation of energy homeostasis and tissue inflammation and to have therapeutic potential for metabolic and inflammatory diseases [ 310 ].…”

Identification of genetic loci associated with higher resistance to pancreas disease (PD) in Atlantic salmon (Salmo salar L.)

“…The members of this gene family are evolutionary conserved and are involved in intracellular signalling networks [28]. The second significant SNP (ssa03: 90,830,374) is an intergenic variant, flanked by a cytokine encoding gene, Metrnl (meteorin-like protein) [29]. The expression of Metrnl is regulated through products of different immune-related genes such as IL-4, IL-12 and IFN-γ, and is associated with inflammation response [29].…”

“…The second significant SNP (ssa03: 90,830,374) is an intergenic variant, flanked by a cytokine encoding gene, Metrnl (meteorin-like protein) [29]. The expression of Metrnl is regulated through products of different immune-related genes such as IL-4, IL-12 and IFN-γ, and is associated with inflammation response [29]. This gene showed an approximately 5-fold elevation in expression among animals that survived the challenge (Supplementary Table 1) compared to those that died early in the trial.…”