Immune regulation of neurodevelopment at the mother–foetus interface: the case of autism

Stefano Sotgiu, Salvatorica Manca, Antonella Gagliano, Alessandra Minutolo, Maria Clotilde Melis, Giulia Pisuttu, Chiara Scoppola, Elisabetta Bolognesi, Mario Clerici, Franca Rosa Guerini, Alessandra Carta

Research output: Contribution to journalReview articlepeer-review

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by deficits in social communication and stereotypical behaviours. ASD’s aetiology remains mostly unclear, because of a complex interaction between genetic and environmental factors. Recently, a strong consensus has developed around ASD’s immune-mediated pathophysiology, which is the subject of this review. For many years, neuroimmunological studies tried to understand ASD as a prototypical antibody- or cell-mediated disease. Other findings indicated the importance of autoimmune mechanisms such as familial and individual autoimmunity, adaptive immune abnormalities and the influence of infections during gestation. However, recent studies have challenged the idea that autism may be a classical autoimmune disease. Modern neurodevelopmental immunology shows the double-edged nature of many immune effectors, which can be either beneficial or detrimental depending on tissue homeostasis, stressors, neurodevelopmental stage, inherited and de novo gene mutations and other variables. Nowadays, mother–child interactions in the prenatal environment appear to be crucial for the occurrence of ASD. Studies of animal maternal–foetal immune interaction are being fruitfully carried out using different combinations of type and timing of infection, of maternal immune response and foetal vulnerability and of resilience factors to hostile events. The derailed neuroimmune crosstalk through the placenta initiates and maintains a chronic foetal neuroglial activation, eventually causing the alteration of neurogenesis, migration, synapse formation and pruning. The importance of pregnancy can also allow early immune interventions, which can significantly reduce the increasing risk of ASD and its heavy social burden.

Original languageEnglish
Article numbere1211
JournalClinical and Translational Immunology
Volume9
Issue number11
DOIs
Publication statusPublished - 2020

Keywords

  • autism spectrum disorder
  • autoimmunity
  • gestation
  • inflammation
  • maternal immune activation
  • neurodevelopment

ASJC Scopus subject areas

  • Nursing(all)
  • Immunology and Allergy
  • Immunology

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