Exosomes and microRNA – a new form of remote and bidirectional neuroimmunomodulation?

Background: There exists the well-known crosstalk between brain and immune system, which has much to do with energy regulation in the body. The selfish brain dominates energy distribution in the presence of threats like predators, wounding with haemorrhage, food scarcity, thirst, cold, and heat. The selfish immune system dominates energy allocation during infection and wounding with infection. Often, the two major organ systems selfishly inhibit each other to govern energy self-supply. However, sometimes they can help each other in early situation with threats (immediate mutual assistance). The brain influences the immune system by means of hard-wired nerve fibres and their neurotransmitters and through hormones from brain-controlled endocrine glands. The immune system influences structures of the brain through soluble factors like cytokines, migrating immune cells, and solute receptors (e.g., of cytokines) on sensory nerve fibres. After the appearance of microRNA, this classical view of neuroimmunomodulation needs some revision. Summary: This view of neuroimmunomodulation has recently been expanded by experimental work in stress research [1, 2]. Next to classical connectors of brain and immune system, exosome microRNA may play an outstanding role in this bidirectional crosstalk. This review systematically analyses sources of microRNA in the brain and effects of this microRNA on target immune function. Vice versa, microRNA of distinct immune cells are demonstrated how they might interfere with various brain functions. Messages: This review has the character of a theory that should stimulate new research in order to define – in a single publication - the origin of microRNA in the brain and its influence on the target in immune cells and vice versa. The field of neuroimmunomodulation should include these new microRNA pathways to obtain a full picture of bidirectional interactions between the two selfish organ systems.