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Science 13 April 2007:
Vol. 316. no. 5822, pp. 285 - 288
DOI: 10.1126/science.1137221
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Reports

Lymphotoxin ß Receptor–Dependent Control of Lipid Homeostasis

James C. Lo,1* Yugang Wang,2* Alexei V. Tumanov,2* Michelle Bamji,3 Zemin Yao,3 Catherine A. Reardon,2 Godfrey S. Getz,2{dagger} Yang-Xin Fu1,2{dagger}

Hyperlipidemia, one of the most important risk factors for coronary heart disease, is often associated with inflammation. We identified lymphotoxin (LT) and LIGHT, tumor necrosis factor cytokine family members that are primarily expressed on lymphocytes, as critical regulators of key enzymes that control lipid metabolism. Dysregulation of LIGHT expression on T cells resulted in hypertriglyceridemia and hypercholesterolemia. In low-density lipoprotein receptor–deficient mice, which lack the ability to control lipid levels in the blood, inhibition of LT and LIGHT signaling with a soluble lymphotoxin ß receptor decoy protein attenuated the dyslipidemia. These results suggest that the immune system directly influences lipid metabolism and that LT modulating agents may represent a novel therapeutic route for the treatment of dyslipidemia.

1 Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
2 Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
3 Department of Biochemistry, Microbiology and Immunology, University of Ottawa Heart Institute, Ottawa, Ontario K1H 8M5, Canada.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: yfu{at}uchicago.edu (Y.-X.F.); getz{at}bsd.uchicago.edu (G.S.G.)

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