Spencer Chen, PhD, Postdoctoral Fellow Memorial Sloan Kettering Cancer Center Area of Research: All Cancers The ever-shifting diversity of luminal antigens at the gastrointestinal interface necessitates a careful balance between immune activation and tolerance. Suppression and coordination of intestinal immune responses are controlled by a population of specialized regulatory T cells (Tregs), with pleiotropic functions in dampening immune responses and promoting tissue repair. However, an understudied player in mediating host-microbe segregation is the population of microfold (M) cells, a specialized intestinal epithelial cell type that samples and delivers antigens to immune cells in the underlying tissue. M cells are crucial to immune surveillance and have been implicated in intestinal inflammatory disorders. However, it is poorly understood how M cell sampling and maintenance are regulated. Since chronic inflammation results from maladaptive immune responses to microbial and dietary antigens, Dr. Chen hypothesizes that dysregulation of M cell sampling and Treg immunosuppression may constitute a hitherto undescribed circuit that underlies the development of inflammation. He will test this hypothesis by using cutting-edge microscopy, spatial, and ‘omics’ techniques to investigate how distinct Treg subsets and functionalities maintain M cells in homeostasis and inflammation (Aim 1). Dr. Chen will determine whether M cells act reciprocally to regulate the induction of Treg and T effector responses and functions in diverse settings through the development of a novel M-cell mouse model (Aim 2). Lastly, he will explore the therapeutic potential of modulating this Treg-M-cell circuit in a Crohn’s disease model (Aim 3). The outcome of this work will be a mechanistic understanding of an unexplored lymphocyte-epithelial circuit, whose dysfunction potentially underlies the development of intestinal inflammatory disorders and cancer. Projects and Grants Lymphocyte-epithelial interactions in intestinal health and disease Memorial Sloan Kettering Cancer Center | All Cancers | 2024 | Alexander Rudensky, PhD
