Intercellular Arc Signaling Regulates Vasodilation
June Bryan de la Peña, Paulino Barragán‐Iglesias, Tzu‐Fang Lou, Nikesh Kunder, Sarah Loerch, Tarjani Shukla, Lokesh Basavarajappa, Jane Song, Dominique James, Salim Megat, Jamie K. Moy, Andi Wanghzou, Pradipta Ray, Kenneth Hoyt, Oswald Steward, Theodore J. Price, Jason D. Shepherd, Zachary T. Campbell
Abstract
Nociceptors play prominent roles in pain and inflammation. We examined rapid changes in the landscape of nascent translation in cultured dorsal root ganglia (DRGs) treated with a combination of inflammatory mediators using ribosome profiling. We identified several hundred transcripts subject to rapid preferential translation. Among them is the immediate early gene (IEG) Arc. We provide evidence that Arc is translated in afferent fibers in the skin. Arc-deficient mice display several signs of exaggerated inflammation which is normalized on injection of Arc containing extracellular vesicles (EVs). Our work suggests that noxious cues can trigger Arc production by nociceptors which in turn constrains neurogenic inflammation in the skin.