Figure 2.

Maternal immune activation. MIA is associated with an increased risk of NDDs in the fetuses. One of the important cytokines for MIA is IL-17, which is produced mainly by Th17 cells. The gut microbiota is able to affect IL-17a levels and mucosal immunity as a whole by regulating the balance between Th17 cells and Treg cells. Besides, the production of IL-17 is also stimulated by elevated IL-6 levels during inflammation in pregnant females. Based on evidence from animal models, inside the CNS, IL17RA is located predominantly in the cortical neurons of S1DZ and elevated IL-17a levels lead to overactivation in these neurons, which then induces abnormalities in terms of social behaviors in MIA offsprings. Another important cytokine is IL-6. IL-6 not only affects the activation of Th17 cells, as is discussed above, but also affects neurons themselves by inducing transcriptional synaptogenesis through STAT3-dependent production of RGS4, which increase glutamatergic synapse density and disrupt hippocampal connectivity.