Study Identifies RNA Molecule That Acts as Brake on Inflammation

Researchers at have identified an RNA molecule, known as a long noncoding RNA, that is responsible for controlling innate immune processes by making sure inflammatory genes in macrophages are switched off until needed.

The study, “A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation,” published in the journal Cell, demonstrated that such long noncoding RNA molecules, commonly called lincRNAs by scientists, should be investigated in inflammatory disease states where the innate immune system is too active, such as in systemic lupus erythematosus (SLE).

“These findings suggest that there is an unexplored layer of regulation controlling inflammatory and immune responses,” Katherine A. Fitzgerald, PhD, senior author of the study and a professor of medicine at University of Massachusetts Medical School, said in a news release.

Recent decades have brought a boom in research into various roles of RNA molecules. Today, several types of RNAs, not involved in the production of proteins, are known, and studies into their roles keep adding to knowledge about the complexities of gene regulation, particularly in the immune system.

Fitzgerald and her research team homed in on a molecule called lincRNA-EPS, and studied how it contributes to the workings of the immune system by removing it from mice. They discovered that macrophages — one of the immune cells involved in launching inflammatory immune responses — produced the linkRNA to prevent the activation of inflammatory genes. But when macrophages encounter a threat, such as an invading microbe, the production of this long noncoding RNA is blocked, allowing inflammatory factors to kick in. Mice that lacked the linkRNA had such high levels of cytokines and other inflammatory molecules they ended up in toxic shock.

As expected, the research team also found that the RNA molecule is controlled by other factors. “We have also found that the expression of lincRNA-EPS itself is very carefully regulated and is very sensitive to slight changes,” said Maninjay K. Atianand, PhD, a postdoctoral fellow at the medical school and first author of the study. “This lincRNA is an important component in the molecular circuitry to prevent spontaneous activation of key immune genes. These findings have important implications for the potential role that lincRNAs may play in chronic inflammation and immune pathologies.”