IWK Health researchers have identified a lipid thought to be a marker for inflammatory diseases such as arthritis. The discovery may help identify potential targets for therapy of inflammatory diseases as well as possible metabolic markers that may indicate where such diseases exist.
The study, “Modulation of the cell membrane lipid milieu by peroxisomal ß-oxidation induces Rho1 signaling to trigger inflammatory responses,” was recently published in Cell Reports.
Lab tests using fruit flies, an organism with immune cells similar to humans, were instrumental in the research. During those tests, lipids were identified within activated macrophages, those white blood cell that surround and kill microorganisms, remove dead cells, and stimulate the action of other immune system cells.
“It was very exciting to validate in human patients that a basic research discovery coming from the humble fruit fly has medical and potential translational relevance,” says Dr. Francesca Di Cara, lead investigator and a pediatric immunology researcher at IWK Health. “This research is still a basic immunology investigation, but it paves the way to investigate alternative drugs that modify distinct metabolic pathways to treat inflammatory diseases.”
Di Cara studies how changes in metabolism in immune cells drive immune cells activation and resolution of core immune responses during infection. Di Cara’s team focuses on lipid metabolisms (fats) and specifically the lipid metabolism that the organelle, peroxisome, produces and removes to regulate immune cells’ behaviour.
“The peroxisome produces and metabolizes both proinflammatory and anti-inflammatory mediators in pediatric diseases characterized by hyperinflammation,” says pediatric immunologist Dr. Beata Derfalvi. “This new discovery about peroxisomes will improve our understanding of inflammation regulation in general.“
Di Cara and Derfalvi will continue to investigate the relevance of the identified signaling in other patients affected by genetic mutations that have resulted in an increased susceptibility to infectious disease, autoinflammatory disease, allergy, or autoimmunity.