Abstract
Mechanisms on how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reporter gene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion. In vitro purified secreted extracellular vesicles (EVs) from blood cells contain Cre mRNA which induces recombination in neurons when injected into the brain.
Highlights
The influence of the immune system on the brain in the context of inflammation is highly relevant for a number of diseases, yet mechanisms for this interaction are not fully understood
By using a genetic tracing system, we show that extracellular vesicles, small membrane structures that can contain a multitude of different molecules, can transfer functional RNA directly from blood cells to neurons
The number of fusion events is very low in the healthy animal, peripheral inflammation induces cell fusion events to increase by a factor of 10–100, giving the first indication that heterotypic fusion is regulated by a pathologic stimulus and may be of biological significance [5]
Summary
The influence of the immune system on the brain in the context of inflammation is highly relevant for a number of diseases, yet mechanisms for this interaction are not fully understood. The stereotypical response is the secretion of proinflammatory cytokines by immune cells. These peripheral cytokines in turn can have a direct effect on neural cells or activate brain inflammatory cytokine signaling, usually via microglia, the principle innate immune cells of the brain [1]. Heterotypic cell fusion of hematopoietic cells with Purkinje neurons in the brain has been suggested as a conceptually different mechanism of response to inflammation. Seen as evidence for an unexpected differentiation potential of hematopoietic stem cells, it was eventually demonstrated that the experimentally observed plasticity was largely attributable to cell fusion, rather than transdifferentiation [2,3,4]
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