Grant: CIHR Fellowship

Maintenance of human health requires an intricate control of the immune response. Generally, inflammatory responses are generated to protect against foreign molecules/pathogens (antigen) and immunological tolerance is reserved for responses to harmless antigen. Gestation is an interesting case where the fetus is, in part, "foreign" to the mother's immune system, although a tolerogenic response is critical for success of the pregnancy. Aberrant induction or loss of tolerance to foreign antigen has the potential to issue life-threatening consequences. For example, cancer metastasis occurs through the induction of tolerance towards cancer cells. Despite a critical role of immunological tolerance throughout human health, the process through which tolerance is acquired remains poorly defined. Thus, the objective of this research is to elucidate the immunological program through which foreign antigen tolerance is generated. This will be studied in the context of human gestation with emphasis placed on defining the immunological landscape within uterine lymph nodes of pregnant females. To explore this program, we will employ a multimodal approach including use of multiplexed ion beam imaging (MIBI), single-cell transcriptomics and epigenetics, and when applicable, mouse models. This approach will provide a comprehensive understanding on the lymph node microenvironment associated with maternal-fetal tolerance and the transcriptional program that may drive the tolerant phenotype. Understanding how tolerance to foreign antigen is acquired is of the utmost importance to guide the development of novel approaches to therapeutically induce or abolish tolerance in disease settings.