Neuroimmune Mechanisms of Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) are characterized by alterations in typical brain development. The immune system is increasingly implicated in NDDs and may contribute to both susceptibility and pathology. Here, we discuss evidence in animal models implicating immune cells and signals in important refinement and modulatory roles in the healthy, developing brain. We review clinical evidence for immune dysfunction in NDDs, including rare immunogenetic disorders with neurodevelopmental impacts, focusing on type I interferonopathies. We also consider data from human and animal models illustrating that early-life immune challenges, including viral infection, may disrupt normal developmental processes and compound genetic predisposition to elevate the risk of developing NDDs. Altogether, these data reveal a clear role for the immune system in brain development in animal models and correlations between immune activation and the onset, progression, or severity of specific NDDs. Closing the gap between these 2 lines of evidence to identify specific immune challenges or signaling pathways that are relevant to human diseases will be essential for future diagnostics, therapeutics, and translational insights.