Immunity raises cholesterol

Our immune system is trying to give us a heart attack. Findings from James Lo, Yugang Wang, Godfrey Getz, Yang-Xin Fu (University of Chicago, IL), and colleagues reveal that T cells hinder the liver's ability to remove cholesterol from the blood.

The immune system and the liver were previously linked by a mouse model of inflammation that causes the animals to have enlarged livers. These mice express high levels of proinflammatory molecules called LIGHT and LT on their T cells. The authors now find that LIGHT-expressing T cells bump up triglyceride and cholesterol levels in the mouse bloodstream.

These lipids are normally broken down by the liver. But T cells carrying LIGHT caused liver cells to make less hepatic lipase, which hydrolyzes triglycerides and phospholipids. Interfering with LIGHT's ability to bind to its LTβR receptor on liver cells lowered cholesterol levels, even in mice that did not have high LIGHT levels to begin with.

High cholesterol is also caused by genetic diseases linked to the loss of the low-density lipoprotein receptor. The group found that mice lacking this receptor also benefit from the blockade of LIGHT signaling. A practical means to thwart LIGHT in humans has not yet been devised. Whether the high risk of heart disease associated with autoimmune diseases is also caused by LIGHT remains to be seen.

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