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Neuromodulation by the immune system: a focus on cytokines

Journal

NATURE REVIEWS IMMUNOLOGY
Volume 21, Issue 8, Pages 526-541

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41577-021-00508-z

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Funding

  1. US National Institutes of Health [MH108156, AT010416, AG034113]

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Interactions between the immune system and the nervous system play a crucial role in shaping host behavior and nervous system function. These interactions may have evolved to maximize an organism's ability to respond to environmental threats. The immune system relays information to the nervous system through cytokine signaling, and the brain may be hardwired to process information from the immune system in a specific way.
Interactions between the immune system and the nervous system have been described mostly in the context of diseases. More recent studies have begun to reveal how certain immune cell-derived soluble effectors, the cytokines, can influence host behaviour even in the absence of infection. In this Review, we contemplate how the immune system shapes nervous system function and how it controls the manifestation of host behaviour. Interactions between these two highly complex systems are discussed here also in the context of evolution, as both may have evolved to maximize an organism's ability to respond to environmental threats in order to survive. We describe how the immune system relays information to the nervous system and how cytokine signalling occurs in neurons. We also speculate on how the brain may be hardwired to receive and process information from the immune system. Finally, we propose a unified theory depicting a co-evolution of the immune system and host behaviour in response to the evolutionary pressure of pathogens. In this Review, Kipnis and colleagues explain how signals from the immune system can shape host behavioural responses, even in the absence of infection or disease. In particular, the authors focus on the cytokine pathways that modulate behavioural responses and consider the evolutionary basis of these neuroimmune interactions.

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