During pregnancy and lactation, mothers undergo dramatic physiological changes to support and adapt to the growing offspring. Epidemiological data suggested that maternal environmental exposure during pregnancy, particularly infection, can shape offspring immunity long term. Additionally, patients with autoimmune diseases experience symptom reduction during pregnancy, while breastfeeding has been linked to increased risk of postpartum relapses. Despite these significant clinical and societal implications, the mechanisms underlying maternal-offspring immune crosstalk remain poorly understood.
Our research aims to understand how maternal environmental exposures impact long-term offspring immunity, and reciprocally, how maternal immunity adapts during pregnancy, lactation and long-term postpartum in humans. As establishing human cohorts takes time and tissue immune profile is ethical challenging to study especially during reproduction, we initially used mouse models to explore mechanisms potentially relevant to human health. In our model system, we uncovered a previously unrecognized role for immune system in strengthening barrier function throughout reproduction. Remarkably, these changes persist after lactation, indicating a durable immune remodeling. These findings helped shape our hypotheses for human-focused research.
Given the limited human data in this area, we propose to analyze UK Biobank data to investigate long-term maternal-offspring health in human. We will compare multi-aspect data (e.g. immune cell populations, proteomics, blood assays, and clinical records) across 3 main groups: Never-pregnant (nulliparous) vs. previously pregnant and lactating females. By identifying immune signatures, disease associations (infection and cancer status) and shifts across reproductive stages, our study will uncover potential conserved features of maternal immune adaptation.
