TY - JOUR
T1 - Immune regulation of neurodevelopment at the mother–foetus interface
T2 - the case of autism
AU - Sotgiu, Stefano
AU - Manca, Salvatorica
AU - Gagliano, Antonella
AU - Minutolo, Alessandra
AU - Melis, Maria Clotilde
AU - Pisuttu, Giulia
AU - Scoppola, Chiara
AU - Bolognesi, Elisabetta
AU - Clerici, Mario
AU - Guerini, Franca Rosa
AU - Carta, Alessandra
N1 - Funding Information:
This work was supported by Ricerca Corrente 2018 and Ricerca Finalizzata 2013: RF‐2013‐02358607, Italian Ministry of Health. Thanks to Elisa Sotgiu and Thomas Leonard‐Roy, Departments of Comparative Literature and English, Harvard University, Cambridge, MA (USA), for help with proofreading.
Publisher Copyright:
© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - autism spectrum disorder
KW - autoimmunity
KW - gestation
KW - inflammation
KW - maternal immune activation
KW - neurodevelopment
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U2 - 10.1002/cti2.1211
DO - 10.1002/cti2.1211
M3 - Review article
AN - SCOPUS:85096573776
VL - 9
JO - Clinical and Translational Immunology
JF - Clinical and Translational Immunology
SN - 2050-0068
IS - 11
M1 - e1211
ER -