Transfer RNA fragments replace microRNA regulators of the cholinergic poststroke immune blockade
Katarzyna Winek, Sebastian Lobentanzer, Bettina Nadorp, Serafima Dubnov, Claudia Dames, Sandra Jagdmann, Gilli Moshitzky, Benjamin Hotter, Christian Meisel, David Greenberg, Sagiv Shifman, Jochen Klein, Shani Shenhar‐Tsarfaty, Andreas Meisel, Hermona Soreq
Abstract
Significance Ischemic stroke triggers peripheral immunosuppression, increasing the susceptibility to poststroke pneumonia that is linked with poor survival. The poststroke brain initiates intensive communication with the immune system, and acetylcholine contributes to these messages; but the responsible molecules are yet unknown. We discovered a “changing of the guards,” where microRNA levels decreased but small transfer RNA fragments increased in poststroke blood. This molecular switch may rebalance acetylcholine signaling in CD14 + monocytes by regulating their gene expression and modulating poststroke immunity. Our observations point to transfer RNA fragments as molecular regulators of poststroke immune responses that may be potential therapeutic targets.