Ai Ing Lim
Optimal development of the 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 exposures during pregnancy, particularly infection, can shape the offspring’s immunity in the long term. During this critical window, the mother also undergoes dramatic immunological changes to nurture and adapt to the semi-allograph fetus. Despite the 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 infection impacts offspring’s long-term tissue-specific immunity and predisposition to immune disorders. Our motivation to study the developmental remodeling of tissue immunity in the context of maternal infection is to determine the etiology of immune disorders. Our goal is also to interrogate how interactions with microbes, in the form of pathogens or commensal, contribute to the evolution and sophistication of our immune system, with the ultimate goal to improve health trajectories in children. While the first part of my program will focus on the maternal impact on offspring, we are also eager to explore reciprocal interaction. Notably, how does maternal immunity adapt to support the physiological changes during pregnancy and lactation. Together, this program is highly relevant to human health and this line of research is essential to pave the way to mitigate pregnancy complications, prevent and treat immune disorders that are rising in the human population. Using multidisciplinary approaches combining infectious diseases, immunology, host-microbes interaction, and developmental biology, we will (1) explore the role of maternal helminth infection on offspring tissue immunity and predisposition to immune disorders; (2) dissect the impact of maternal infection on breastmilk composition and function; and (3) understand mechanisms of maternal immune adaptation to pregnancy and lactation.
Maternal-offspring crosstalk is a fundamental line of research with profound implications for women’s and children’s health. Paradoxically, such important question has been neglected and stymied by inequities in science. We are striving to understand this rudimentary crosstalk not only for the urgent need to improve women’s and children’s health through rigorous basic research, but also to overcome such longstanding inequities and bias in science.
Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring. Science. 2021 ;373(6558). .
Pre-birth memory. Nat Immunol. 2019 ;20(3):254-256. .
Developmental options and functional plasticity of innate lymphoid cells. Curr Opin Immunol. 2017 ;44:61-68. .
Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation. Cell. 2017 ;168(6):1086-1100.e10. .
IL-12 drives functional plasticity of human group 2 innate lymphoid cells. J Exp Med. 2016 ;213(4):569-83. .
Ai Ing Lim is an incoming Assistant Professor of Molecular Biology at Princeton University. Originally from Malaysia, she received her master’s degree from The University of Hong Kong. As a European Union Marie Curie Fellow, she completed her graduate studies at Pasteur Institute (Paris), under the mentorship of Prof. James Di Santo. There, she identified innate lymphocyte precursors from the blood and tissues of healthy individuals. With the support of Human Frontier Science Program fellowship, she joined the laboratory of Dr. Yasmine Belkaid at the National Institutes of Health for postdoctoral training. During her postdoctoral training, she found that maternal infection can provide pre-birth immune education to the offspring in a tissue-specific manner. Together, her works in both human and murine immunology demonstrated that the immune system is highly plastic and can adapt to environmental challenges even before birth. Her contributions were recognized as an International Rising Talents by the L’Oreal-UNESCO, the best European Immunology Thesis (ACTERIA Doctoral Prize) by the European Federation of Immunological Societies, the Sidney & Joan Pestka Post Graduate Award by the International Cytokine and Interferon Society.