A new study published by researchers at UC Santa Cruz uncovers the mechanism that regulates the expression of genes in immune systems cells. Macrophages are first-responder immune cells that specialize in the detection and destruction of harmful substances in the body.

The new research has pinpointed the exact long noncoding RNA (IncRNA) that regulates the expression of pro-inflammatory genes in immune cells. Offering an insight into future research that could paint a clear picture of how therapies could be developed in this area to prevent conditions such as sepsis.

The lncRNA discovered is called GAPLINC, a molecule previously studied in cancer patients. This new study has discovered that GAPLINC is highly expressed in macrophages. Previous studies have shown that removing GAPLINC protected mice from endotoxic shock.

Conversely, for mice with sepsis, eliminating GAPLINC led to death within 24 hours.

GAPLINC is one of the few examples of a lncRNA found in both humans and mice.

Susan Carpenter, assistant professor of molecular, cell, and developmental biology at UC Santa Cruz explains:

“Our hypothesis was that the knockout mice would do worse in a model of endotoxic shock, so we were surprised to find that they did much better.”

Macrophages are found in the blood as monocytes. Monocytes are white blood cells that play an important role in the immune response, as well as facilitating healing and repair. Carpenter found that macrophages help turn on inflammation.

But contrary to popular belief, they also play an important role in turning it off again. In sepsis, the immune system activity is exponentially heightened.

Leading to a cytokine storm, a process that’s involved in blood clotting and inflammation. The problem arises when this system is out of control and the blood clotting blocks the flow of blood to the vital organs.

Carpenter concluded:

“We are a long way from understanding how you would target this therapeutically, but at least we have identified a pathway to home in on.”

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