Exploring the role of Gamma Delta T cell subsets in chronic liver and bowel inflammation (360G-Wellcome-203825_Z_16_A)

Chronic inflammation in the liver/bowel accounts for a large proportion of inflammatory diseases and causes significant morbidity and mortality. Whilst chronic inflammation is thought to stem from immune hyperactivation and failure of immunosuppressive pathways, much of this research is based on conventional lymphocytes such as alphabeta T cells and B cells. Unconventional T cell subsets such as gammadelta T cells are thought to also have a role in effector responses and immune regulation. They are enriched in liver and bowel tissue and can be potent producers of inflammatory cytokines. We aim to explore the dysregulation of gammadelta T cell function in chronic inflammatory conditions and how it aligns with conventional adaptive responses and other unconventional T cells such as Mucosal Associated Invariant T cells (MAITs) and invariant Natural Killer T cells (iNKTS). Using in vitro functional assays and molecular immunophenotyping techniques we will determine the phenotype of unconventional T cells in normal and inflamed human liver/bowel samples. We will also use mouse inflammation models to study the response of these cells to inflammatory stimuli. These studies will unravel the role of unconventional T cells in chronic inflammatory responses and may identify potential therapeutic avenues for suppression of unconventional inflammatory responses.