Isoketals are highly reactive oxidation products of arachidonic acid that can form adducts with cellular proteins. In the Journal of Clinical Investigation, Harrison and colleagues link the production of isoketals to stimulation of the immune system and hypertension. Dendritic cells (DCs) in an angiotensin-induced model of mouse hypertension show signs of oxidative stress and develop enrichment for isoketals. The isoketals in these DCs generate neoantigens, which can be recognized by T cells as non-self. In addition, the isoketal-containing DCs upregulate the costimulatory molecules CD80 and CD86, as well as the cytokines IL-6 and IL-23, and therefore efficiently activate T cells to proliferate and produce proinflammatory cytokines. Chemical inhibition of isoketal activity not only prevents the stimulation of the immune system but also ameliorates the hypertension in this model. These findings therefore suggest new ways of modulating the pathological activation of the immune system that results from oxidative damage.

J. Clin. Invest. (17 September 2014) doi:10.1172/JCI74084