Maternal inflammation promotes autoimmune susceptibility in offspring

Maternal immune activation during pregnancy poses a unique health risk to offspring. prenatal exposure to inflammation or other stressful conditions have been shown to adversely impact brain development, leading to abnormal behavioral outcomes later in life. However, whether exposure to inflammation during pregnancy could also alter the offspring's immune system to render it more susceptible to dysregulation later in life is left unaddressed. Here we report that adult offspring, prenatally exposed to MIA, become more susceptible to developing colitis-like phenotypes. This enhanced susceptibility was accompanied by increases in the production of inflammatory cytokines, such as interleukin-17a and interferon-gamma, and associated alterations in the epigenomic landscape of CD4 T cells. Furthermore, we show that the changes in the offspring's immune system require maternal IL-17a and are driven by the changes in the maternal gut microbiota. Altogether, our study suggests that children, exposed to heightened inflammation in the maternal womb following viral infection or due to other inflammatory conditions, are at a higher risk to develop autoimmune diseases, including inflammatory bowel diseases, later in life.