Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors

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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.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalBrain, Behavior, and Immunity
Volume31
DOIs
StatePublished - Jul 2013

Fingerprint

Myeloid Cells
Amygdala
Dendritic Cells
Chemokines
Immune System
Cytokines
Autism Spectrum Disorder
Antigen Presentation
Microglia
Autistic Disorder
Phagocytosis
Innate Immunity
Monocytes
Macrophages
T-Lymphocytes
Brain

Keywords

  • Amygdala volume
  • Autism
  • Dendritic cells
  • Innate immunity
  • Repetitive behaviors

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

Cite this

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title = "Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors",
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 na{\"i}ve 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.",
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author = "Elizabeth Breece and Brian Paciotti and Nordahl, {Christine W} and Ozonoff, {Sally J} and {Van de Water}, {Judith A} and Rogers, {Sally J} and Amaral, {David G} and Paul Ashwood",
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AU - Breece, Elizabeth

AU - Paciotti, Brian

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AB - 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.

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