Memorial Sloan Kettering Cancer Center
Project Title: Acceptance of Non-Self: Decoding Intestinal Immune Tolerance During Early Life
Award Year: 2022
Biography
The goals of Dr. Brown’s research program are to understand how signals from the tissue environment shape the fate and function of immune cells and the mechanisms by which the immune system reciprocally regulates tissue homeostasis and host immunity. Studies center on antigen-presenting cells, sentinels of the immune system that play a critical role in shaping the differentiation and function of effector and regulatory T cells. Recent work from the lab defined the cell types and mechanisms that instruct peripheral regulatory T cell development and tolerance to the gut microbiota during early life. This work uncovered a novel lineage of peripheral antigen-presenting cells, named Thetis cells, with transcriptional homology to Aire-expressing medullary thymic epithelial cells, highlighting parallels between mechanisms of thymic and peripheral tolerance. Ongoing work addresses how the tissue microenvironment and microbiota shape immune development, and the mechanisms by which diverse antigen-presenting cell types instruct tolerance to self and foreign antigens vs. immunity to pathogens.