Transfer RNA fragments replace microRNA regulators of the cholinergic post-stroke immune blockade II

After ischemic stroke, the brain initiates intensive communication with the immune system, and acetylcholine contributes to this process. Stroke triggers peripheral immunosuppression leading to increased susceptibility to infections; and post-stroke pneumonia is linked with poor stroke outcome, but the responsible processes are yet unknown. We discovered a “change of guards” where microRNA levels decreased but small transfer RNA fragments (tRFs) accumulated in post-stroke blood cells. This molecular switch may re-balance acetylcholine signaling in CD14+ monocytes by regulating their gene expression and modulating post-stroke immunity. Our observations point to tRFs as new molecular regulators of post-stroke immune responses that may become potential therapeutic targets. PolyA-selected long RNA sequencing from whole blood of ischemic stroke patients two days post stroke and age matched controls