Immune System Dynamics in Pregnancy

The maternal immune system undergoes a finely tuned sequence of adaptations throughout gestation, balancing tolerance towards the semi-allogeneic fetus with defence against pathogens. Early implantation is accompanied by a pro-inflammatory milieu that enables trophoblast invasion and placental remodelling. This shifts in mid-pregnancy towards an anti-inflammatory environment to support rapid fetal growth, before reverting to a second pro-inflammatory phase that facilitates labour. Innate immune cells, including decidual natural killer cells and macrophages, interact with adaptive T-helper subsets to orchestrate local responses, while systemic cytokine profiles reflect and sometimes diverge from these tissue-specific changes. Maternal factors such as parity, body mass index and metabolic status further shape immune trajectories. Understanding these dynamics is essential for elucidating the pathogenesis of complications such as pre-eclampsia, preterm birth and gestational hypertension, and for informing targeted immunomodulatory strategies.

Research from Nature Portfolio

Recent studies have demonstrated that maternal immune adaptation is modulated by previous pregnancies and adiposity. A longitudinal analysis of stimulated peripheral blood mononuclear cells and serum biomarkers revealed a dampening of cellular cytokine responses—such as TNF-α, IL-10 and IFN-γ—from early to late gestation, while circulating markers including IL-6, IL-17A and complement C3 increased. These changes varied significantly with parity and body mass index, offering mechanistic insight into why first-time mothers and individuals with elevated BMI face higher risks of placental disease. Foundational work using high-sensitivity proximity extension assays has further charted the transition from late pregnancy to early postpartum, showing that most inflammatory and anti-inflammatory proteins decrease after delivery, whereas a small subset of cytokines rises, reflecting the immunological reset that follows parturition.

Immune System Dynamics in Pregnancy publication trend

The graph below shows the total number of articles in immune system dynamics in pregnancy across all publications each year (not limited to Nature Index journals).

Technical terms

Cytokine: A signalling protein secreted by immune cells to regulate inflammation and cell communication.

Peripheral blood mononuclear cell (PBMC): A blood cell type, including lymphocytes and monocytes, used to study cellular immune responses.

Soluble fms-like tyrosine kinase-1 (sFLT1): A circulating anti-angiogenic factor that modulates vascular development and inflammation at the maternal-fetal interface.

Macrophage migration inhibitory factor (MIF): A multifunctional cytokine involved in innate immunity, inflammation and regulation of other cytokines.

Parity: The number of previous pregnancies carried to viable gestational age, which influences maternal immune memory and adaptation.

Mendelian randomisation: A method using genetic variants as proxies for modifiable exposures to assess causal relationships in observational data.

References

1. Impact of previous pregnancy and BMI on cellular and serum immune activity from early to late pregnancy. Scientific Reports (2024).
2. Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum. Scientific Reports (2019).
3. Circulating inflammatory cytokines and hypertensive disorders of pregnancy: a two-sample Mendelian randomization study. Frontiers in Immunology (2023).
4. MIF Increases sFLT1 Expression in Early Uncomplicated Pregnancy and Preeclampsia. International Journal of Molecular Sciences (2023).
5. IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. International Journal of Molecular Sciences (2022).