Work

Prenatal maternal stress induces gut microbiota dysbiosis and long-term programming of autoreactive CD4 T cells in the context of neuroinflammation 2132

Year: 2025

Type: article

Abstract: Description The prenatal period is a sensitive time during which intrauterine exposure to environmental factors can shape the developing immune system in offspring. Evidence suggests that maternal stress during pregnancy weakens adaptive immune responses in offspring, increasing their risk of infectious diseases and cancer. However, the mechanisms through which prenatal stress (PS) impairs immune responses in adulthood are not fully understood. To address this knowledge gap, we developed a PS animal model where pregnant females experience stress during a specific gestational period. We examined the effect of PS on autoimmune responses in adult offspring using experimental autoimmune encephalomyelitis, a well-suited model for studying T lymphocyte functions. Our findings indicate that PS reduces the pathogenic potential of CD4 T cells by limiting their production of inflammatory cytokines and their ability to infiltrate the central nervous system. Adoptive transfer experiments confirmed that PS has a stable and intrinsic effect on CD4+ T cells, potentially due to epigenetic changes. We found that this effect is linked to intestinal dysbiosis and identified a microbiota metabolite that may play a role. Overall, our study demonstrates that PS leaves a lasting “immune imprint” on CD4 T cell function, associated with microbiota dysbiosis. The discovery of a relevant metabolite could serve as a potential therapeutic target for multiple sclerosis patients. Funding Sources Supported by INSERM, ARSEP and FRC Topic Categories Neuroimmunology (NEUR)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.094