Maternal vitamin D regulates the metabolic rearrangement of offspring CD4+ T cells in response to intestinal inflammation.

Children with autism spectrum disorders often have increased susceptibility to intestinal inflammation. However, the mechanisms and prevention of gastrointestinal immune dysfunction remain unclear. We demonstrate that maternal high vitamin D (VitD) level can rescue abnormal intestinal immune phenotypes in offspring that exhibit autism-like phenotypes due to exposure to maternal inflammation. Offspring exposed to dual insult of maternal inflammation and VitD deprivation show increased susceptibility to intestinal inflammation. Maternal high VitD level altered the metabolic patterns and chromatin accessibility of offspring CD4+ T cells and rescued the abnormal immune state of offspring induced by maternal immune activation (MIA). Additionally, MIA has long-term impacts on the immune phenotype of offspring in the second litter. Our findings suggest why exposure in utero to high inflammation and low maternal VitD levels increase the risk of inflammatory diseases in offspring.