Research

Maternal-Offspring Immune Partnerships

Mothers and offspring are evolutionary partners. From gestation to lactation, mothers undergo profound immunological transformations that are essential to tolerate and nurture semi-allograph offspring, while simultaneously responding to environmental challenges. A growing body of epidemiological data shows that maternal exposure to environmental factors, from pathogens to pollutants, can markedly influence offspring immune system development, prenatally through the placenta and postnatally through breastfeeding. These influences are not transient but can permanently shape offspring immunity and alter lifelong susceptibility to infection and inflammation.

We aim to define the cellular and molecular mechanisms underlying maternal-offspring immune partnerships by addressing two overarching questions:

How does maternal immunity adapt across reproductive stages, from pregnancy and lactation to postpartum?
How do maternal environmental exposures shape the development of the offspring’s immune system?

Our motivation to study maternal-offspring immune crosstalk is threefold:

To mitigate pregnancy complications and improve women’s health;
To determine the origins of immune disorders and improve long-term health trajectories in children;
To understand how interactions with environmental factors have shaped the evolution and sophistication of the immune system.

Pre-birth Hygiene Hypothesis

Helminths are the most abundant animal species on earth, and mammals' closest evolutionary partners. To date, over a quarter of the world population remains infected with helminths, but this longstanding partnership has been eliminated in high to middle-income countries. The removal of these evolutionary partners has been proposed to contribute in part to the dramatic increase of immune disorders, such as allergies and autoimmune diseases, a model referred to as “hygiene hypothesis”. Building on epidemiological data showing that deworming treatment during pregnancy increases risks for infantile eczema, we hypothesize that maternal helminth partnership controls offspring immunity and reduces susceptibility to immune disorders, termed as “pre-birth hygiene hypothesis".
This project is funded by The Branco-Weiss Fellowship.

Breastmilk Composition

Breastmilk is the primary nutrient source to support the growth of infants in early life. Breastmilk also provides passive immunity via transferring immunoglobulins, microbial derivatives, and immune cells to the offspring. The composition of breastmilk is primarily controlled by the maternal intestine for nutrient absorption and by the mammary glands for nutrient synthesis and secretion. The immune status of the breastfeeding mother therefore has vast implications for breastmilk composition and subsequently shaping the infant’s health. We aim to understand how maternal immunological status alters the breastmilk composition and shapes the offspring tissue immunity.

Maternal Immune Adaptation

During pregnancy and lactation, the mother experiences dramatic physiological changes to nurture and adapt to the growing offspring. It has long been appreciated that hormone-mediated immune changes during pregnancy, including the induction of regulatory T cells, help to safeguard fetal development. Epidemiological data also revealed that patients with defined autoimmune diseases can experience reduced autoimmune symptoms during pregnancy, and breastfeeding is associated with postpartum relapses. Despite these observations and the vast clinical implications, the mechanisms underlying the maternal immune adaptation during pregnancy and lactation remain largely unknown. We aim to understand this fundamental physiological adaptation to improve women's health.