The role of mast cells in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) comprises a group of neurodevelopmental disorders characterized by alterations in communication, repetitive behaviors and impaired socialization. The precise etiology and pathogenesis remain unclear, and there is currently no effective treatment for this condition. Emerging research highlights the role of immune dysregulation in ASD pathophysiology. Mast cells (MCs) are immune cells traditionally associated with allergic diseases but also play a crucial role in other inflammatory and immune processes. Increased MC activity may be linked to the development of ASD in certain patients. This review explores the potential mechanisms involving MCs in ASD, including neuroinflammation, autoimmunity, and disruptions in the gut-brain axis. Evidence suggests that MC mediators such as histamine, serotonin, and cytokines influence neuroinflammatory pathways that are altered in ASD, and MCs can interact with other immune and neuronal cells contributing to ASD symptoms. Autoimmunity is frequently present in both ASD patients and their mothers, and MCs could originate these processes by modulation of lymphocyte populations or secretion of self-antigens. Finally, MC involvement in gut permeability and microbiota dysbiosis underscores their role in gastrointestinal comorbidities frequent in ASD. Targeting MC activity through pharmacological agents offers promising therapeutic avenues. This comprehensive review sheds light on immune-mediated processes underlying ASD and discusses potential future strategies for intervention.