Systemic immune system and neuroinflammatory milieu

The systemic immune system and neuroinflammatory milieu refers to the complex, bidirectional communication network between peripheral immune cells and the central nervous system (CNS) (Prinz & Priller, 2014, Nature Reviews Neuroscience). This milieu is characterized by the interaction of circulating leukocytes, systemic cytokines, and the blood-brain barrier with resident CNS cells like microglia and astrocytes (Louveau et al., 2015, Nature). In healthy states, this system maintains neural homeostasis and supports repair; however, chronic dysregulation leads to sustained neuroinflammation, a hallmark of neurodegenerative diseases such as Alzheimer's and Multiple Sclerosis (Tankou et al., 2018, Frontiers in Neurology). Therapeutic strategies often aim to reprogram this environment by inhibiting pro-inflammatory signaling or preventing the infiltration of peripheral immune cells into the brain (Hansson, 2021, Nature Medicine). Because it encompasses a vast array of cell types and signaling molecules, it is considered a physiological context or pathway rather than a single drug target. Understanding this milieu is critical for developing disease-modifying therapies that address the systemic contributions to brain pathology (Mrdjen et al., 2018, Immunity).

Other names

Neuroimmune axisSystemic-CNS immune crosstalkNeuroinflammatory environmentPeripheral-central immune interface

Modulation of systemic immune cell trafficking, cytokine production, and glial activation to alter the inflammatory state of the central nervous system.