Neutralization of IL-15 abrogates experimental immune-mediated cholangitis in diet-induced obese mice.

Sci Rep 2018 02 15;8(1):3127. Epub 2018 Feb 15.

Aspen Woods Clinic, Calgary, Alberta, Canada.

Obesity is a global epidemic affecting chronic inflammatory diseases. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can occur as an extraintestinal manifestation of inflammatory bowel disease (IBD). Previously we reported that patients with PSC who are obese have a higher risk of advanced liver disease. Currently it is unknown how obesity accelerates or worsens PSC. We evaluated the progression of PSC in an antigen-driven cholangitis mouse model of diet-induced obesity. Obesity was induced in our murine model of immune-mediated cholangitis (OVAbil). OVAbil mice were fed standard chow or high-fat/sucrose diet for twelve weeks followed by induction of biliary inflammation by OVA-specific T cell transfer. Histopathological damage in portal tracts was scored and serum collected. Neutralizing antibodies against IL-15 were administered daily until study termination. Obese mice developed exacerbated liver inflammation and damage. Immune cell phenotyping in liver revealed greater numbers of neutrophils and CD8+ T cells in obese mice. Higher levels of cytokines and chemokines were found in obese mice with cholangitis. Immuno-neutralizing antibodies against IL-15 greatly attenuated cholangitis in obese mice. Obesity exacerbated experimental PSC in part by overproduction of IL-15. Timely targeting of IL-15 may slow the progression of PSC.

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http://dx.doi.org/10.1038/s41598-018-21112-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814438PMC
February 2018
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References

(Supplied by CrossRef)

T Tsujimoto et al.
Medicine (Baltimore) 2016

M Chehimi et al.
Adipocyte 2016

JY Huh et al.
Mol Cells 2014

M Ng et al.
Lancet 2014

B Eksteen et al.
Clin Liver Dis 2016

TH Karlsen et al.
Gut 2016

T Folseraas et al.
Clin Liver Dis 2016

X Zhang et al.
Immunity 1998

YH Liou et al.
J Immunol 2014

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