A group of genes that have been largely ignored by scientists could play critical roles in atherosclerosis (hardening of the arteries), inflammation, and likely obesity and other metabolic diseases, new research suggests.

The discovery was made by researchers at the University of Virginia School of Medicine in the context of how our bodies recognize and remove dead cells. "Research came across the genes, called SLCs, kind of by accident," said researcher Kodi Ravichandran, who chairs the Department of Microbiology, Immunology and Cancer Biology. "Initially, just like everybody else, we were not paying much attention to the SLCs.

But they kept coming up repeatedly in our gene expression analyses, and we realized this must be relevant. Then we took a serious dive into their biology, and we had a lot of fun surprises." Physicians could target these SLC genes with drugs to battle inflammation in tissues such as seen in atherosclerosis, rheumatoid arthritis, and colitis, and even to benefit patients undergoing chemotherapy for cancer, the researchers say.

Two postdoctoral fellows in the Ravichandran laboratory, Sho Morioka and Justin Perry, and their collaborators including researchers across UVA and beyond identified a group of 33 SLC genes that help direct how the body disposes of its dying cells. "We turn over about 200 billion cells a day in the body as part of everyday healthy living.

Inflammation

Imagine this as your daily house cleaning essential. Importantly, we do not want the dead trash to induce inflammation," Ravichandran explained. "So the system has designed a beautiful way to consistently remove our cellular trash, and also simultaneously suppress the inflammation against our cellular debris. And to achieve this, the cells talk to each other about how they recognize each other, what they need to eat, and how the neighboring cells should behave afterward."

The 33 SLC genes the researchers identified issue instructions to help the body's trash disposers cells known as phagocytes  deal with dead and dying cells. "When a phagocyte eats another dying cell, basically its contents have doubled, and it has to manage all of this excess metabolic cargo while still maintaining its normalcy," Ravichandran said. "You can imagine this as if you are swallowing your neighbor in whole. Not an easy problem."

The researchers have published their findings in the scientific journal Nature. This paper is the 11th article in this prestigious journal arising from research done at UVA by members of the Ravichandran laboratory. "This speaks to the phenomenal quality of trainees we have been fortunate to attract to UVA and the UVA environment that fosters this type of success," Ravichandran said.