ReviewThe role of immune mechanisms in Tourette syndrome

•Overactive innate and adaptive immune responses are seen in Tourette syndrome (TS).•Active immunization and other immune-based animal models show face validity for TS.•An abnormal immune response to streptococci and other bacteria is observed in TS.•Preliminary preclinical and clinical evidence suggests microglial activation in TS.•Immune-related and neurotransmitter signaling genes are differently expressed in lymphocytes of TS patients.This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.

Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses.This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.