Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors
Brain, Behavior, and Immunity, Volume 31, July 2013, Pages 69–75, Inflammation and Mental Health
Elizabeth Breece1,2, Brian Paciotti2, Christine Wu Nordahl2,3, Sally Ozonoff2,3, Judy A. Van de Water2,4, Sally J. Rogers2,3, David Amaral2,3, and Paul Ashwood1,2,*1Department of Medical Microbiology and Immunology, University of California, Davis, USA2M.I.N.D Institute, University of California, Davis, USA3Department of Psychiatry and Behavioral Sciences, University of California, Davis, USA4Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, USA
Abstract The pathophysiology of autism spectrum disorder (ASD) is not yet known; however, studies suggest that dysfunction of the immune system affects many children with ASD. Increasing evidence points to dysfunction of the innate immune system including activation of microglia and perivascular macrophages, increases in inflammatory cytokines/chemokines in brain tissue and CSF, and abnormal peripheral monocyte cell function. Dendritic cells are major players in innate immunity and have important functions in the phagocytosis of pathogens or debris, antigen presentation, activation of naïve T cells, induction of tolerance and cytokine/chemokine production. In this study, we assessed circulating frequencies of myeloid dendritic cells (defined as Lin-1−BDCA1+CD11c+ and Lin-1−BDCA3+CD123−) and plasmacytoid dendritic cells (Lin-1−BDCA2+CD123+ or Lin-1−BDCA4+ CD11c−) in 57 children with ASD, and 29 typically developing controls of the same age, all of who were enrolled as part of the Autism Phenome Project (APP). The frequencies of dendritic cells and associations with behavioral assessment and MRI measurements of amygdala volume were compared in the same participants. The frequencies of myeloid dendritic cells were significantly increased in children with ASD compared to typically developing controls (p < 0.03). Elevated frequencies of myeloid dendritic cells were positively associated with abnormal right and left amygdala enlargement, severity of gastrointestinal symptoms and increased repetitive behaviors. The frequencies of plasmacytoid dendritic cells were also associated with amygdala volumes as well as developmental regression in children with ASD. Dendritic cells play key roles in modulating immune responses and differences in frequencies or functions of these cells may result in immune dysfunction in children with ASD. These data further implicate innate immune cells in the complex pathophysiology of ASD.
