An immune clock of human pregnancy

Abstract

The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling–based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2–dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.

Why are pregnant women susceptible to COVID-19? An immunological viewpoint

“…Instead of keeping immune suppression, maternal immunological states actively adapt to be changed with the growth and development of fetus at different gestational stage: from a pro-inflammatory state (beneficial to the embryo implantation and placentation) in the first trimester to an antiinflammatory state (helpful for the fetal growth) in the second trimester, and finally reaching a second pro-inflammatory state (preparing for the initiation of parturition) in the third trimester . Recently, Aghaeepour and colleagues (Aghaeepour et al,2017) suggested a precise timing of immunological events in peripheral blood that occurred during full-term pregnancy, named "immune clock." They found that pregnancyinduced a robust and progressive increase in endogenous STAT5ab signaling across J o u r n a l P r e -p r o o f multiple T cell subsets, including CD25 + FoxP3 + Treg cells, naïve and memory CD4 + and CD8 + T cells, and γδ T cells.…”

“…Innate immune cells, such as NK cells and monocytes, respond more strongly to viral challenges, while some adaptive immune responses are down-regulated during pregnancy, e.g. decreased numbers of T cells and B cells (Aghaeepour et al,2017). Besides, during pregnancy, the upper respiratory tract tends to be swollen by a high level of estrogen and progesterone, and restricted lung expansion makes the pregnancy woman susceptible to respiratory pathogens.…”

Biologic mechanisms and clinical consequences of pregnancy alloimmunization

“…10 Although this important study reveals the scale of the immunomodulation that occurs during pregnancy, it remains unknown which of these changes is driven specifically by exposure to fetal alloantigen (ie, alloimmunization) or whether these changes occur because of other antigen nonspecific mechanisms. 10 Although this important study reveals the scale of the immunomodulation that occurs during pregnancy, it remains unknown which of these changes is driven specifically by exposure to fetal alloantigen (ie, alloimmunization) or whether these changes occur because of other antigen nonspecific mechanisms.…”

Impact of pregravid obesity on maternal and fetal immunity: Fertile grounds for reprogramming

“…). Changes in the maternal adaptive immune include decreased Th1/Th17 and increased Th2/Treg responses . Changes in maternal innate immune responses include increased surface expression of CD11a, CD11b, CD49d, CD14, CD64, and CD54 on monocytes during third trimester .…”