Neuromodulation by the immune system: implications for brain-directed immunotherapy

Once believed to be limited in its impact on the brain, the immune system is now recognized as a potent modulator of the brain and behavior. This review explores the evolving understanding of the brain-immune axis, highlighting the role of immune cells and molecules in neuromodulation and behavioral regulation, with a focus on recent findings detailing the influence of immune factors like interleukin (IL)-17A, IL-17E, IL-4, C-C motif chemokine ligand 5, and matrix metalloproteinase 8 on social behavior, learning, memory, and stress susceptibility. The advent of immunotherapy has revolutionized treatments for cancer and autoimmune diseases. Emerging evidence suggests that similar approaches could address neurological and psychiatric disorders by targeting dysregulated brain-immune interactions. A deeper understanding of the complex relationship between the brain and the immune system will be essential for unlocking the therapeutic potential of immunomodulation for brain disorders and positioning the immune system as a key player in restoring mental health.