A single microRNA - tiny RNAs that regulate the expression of protein-coding genes, microRNA-223, in mice controls the production and activation of granulocytes, a type of white blood cells essential for host defense against invading pathogens.  This is the first microRNA shown to play an essential role in the innate immune response, the results published in the February issue of Nature.   Absence of microRNA-223 increased the production, differentiation and activation of granulocytes, causing tissue inflammation and damage. Increased production of microRNA-223 conversely may reduce inflammatory conditions.  This could have potential implications in the pathogenesis of inflammatory diseases such as acute lung respiratory disease syndrome as well as leukemia.  MicroRNA-223 is unique because its expression is entirely restricted to a specific branch of the immune system.  The study showed that microRNA-223 targets Mefc2, a transcription factor that promotes the expansion of granulocyte cell progenitors, and by knocking out Mefc2  some of the effects caused by microRNA-223 were eliminated.  In the study the mice which were modified to lack microRNA-223 expression had up to three times as many granulocytes in their bone marrow and blood. Moreover, the granulocytes matured more rapidly and then reacted more aggressively to stimuli. This increased activity caused tissue inflammation and damage within the lungs, the liver, muscle and kidneys.  Normally once the infection is cleared granulocytes usually migrate away and settle down.   However,  in the mutant mice they didn’t settle down after they were done fighting. Instead they continued an inflammatory response that did more damage.  Since many forms of leukemia express diminished levels of microRNA-223, the research team will investigate how silencing of this microRNA may contribute to the development of that disease.