Research Projects

Inflammatory bowel disease (IBD) is a complex immune disorder characterized by chronic inflammation in the gut. This inflammation is driven by a complex interplay of genetic and environmental factors that disrupt intestinal immune homeostasis. Importantly, these immune perturbations are not confined to the gut but also manifest systemically. Regulatory T cells (Tregs), essential for maintaining intestinal immune balance, are profoundly affected in IBD. While advances in cellular and molecular tools have deepened our understanding of IBD, a comprehensive picture of Treg modulation in human IBD is still lacking. This project aims to address this gap by extensively characterizing Treg modulation using an integrated multiparametric approach. This will include defining a complete immune signature of conventional, effector and regulatory T cells, robustly evaluating the differential expression profile of circulating Tregs, assessing their epigenetic stability, and performing real-time extracellular flux analysis to assess metabolic reprogramming of ex vivo expanded patient Treg cells. This multifaceted analysis will identify distinct mechanisms operative in Tregs in the context of gut inflammation in IBD. Furthermore, to understand how localized gut inflammation leads to systemic Treg modulation, we will investigate the role of extracellular vesicles (EVs). These nanoscale vesicles transport diverse cargo, including genetic material, proteins, and lipids, from their cells of origin to distant target cells. In IBD, EVs have been implicated in modulating innate immune cells. Emerging evidence suggests that EV-encapsulated miRNAs may also regulate peripheral Treg induction and overall Treg function, as observed in other autoimmune diseases including multiple sclerosis and Rheumatoid arthritis. This project aims to decipher the role of circulating EVs in modulation of Treg homeostasis in IBD. We will perform in depth analysis of the proteomic and miRNA profiles of EVs isolated from the plasma of IBD patients. Subsequent in silico analysis and pathway enrichment will identify novel mechanisms by which these EVs influence Treg induction and function. Key predictions from this analysis will be further validated through strategic ex vivo and in vitro experiments. Finally, functional consequence of the validated miRNAs and their target gene axis in Tregs will be tested in an animal model of colitis to elucidate new avenues of Treg immune regulation in IBD.