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Maternal-Offspring Immune Crosstalk

Optimal development of immune system requires defined environmental input in a spatiotemporally regulated manner. This fundamental process begins in utero in parallel to organogenesis. Numerous epidemiological data suggested that maternal environmental exposure during pregnancy, particularly infection, can shape the offspring immunity in the long term. During this critical window, the mother also undergoes dramatic physiological changes to nurture and adapt to the semi-allograph fetus. Despite vast clinical and societal implications, the mechanisms underlying maternal-offspring immune crosstalk remain largely elusive. We aim to establish a mechanistic understanding of how maternal environmental exposure impacts long-term offspring tissue immunity, and reciprocally, how maternal immunity adapts to pregnancy and lactation.

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.

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