Therapeutic Targeting of Group 3 Innate Lymphoid Cells in Inflammatory Bowel Disease to Amino Acid Transport as a Rheostat of Group 2 Innate Lymphoid

Innate lymphoid cells (ILCs) are critical mediators of immunity and inflammation, which are enriched at barrier sites including the lung and gastrointestinal tract. ILCs have the ability to respond rapidly to danger signals, and are integral for maintaining homeostasis and providing host immunity in response to infection. In contrast to these protective roles, hyperactivated ILC responses have been implicated in driving intestinal inflammation and allergic disease. Thus, identifying potential avenues to therapeutically target the ILC family could prove critical in developing new treatments for prevalent inflammatory diseases.

It is increasingly understood that cell intrinsic changes in lymphocyte metabolism are critical not only to generate the energy and biomass required to fuel immune effector function, but in determining the quality and magnitude of immune cell responses. In particular, fundamental metabolic substrates - such as essential amino acids - act to fuel biosynthesis and provide environmental cues that act as a rheostat for cellular metabolic function. Recent advances suggest ILCs are also highly sensitive to changes in nutrient availability and perturbations of cellular metabolism. As a result there is significant interest in understanding the role of metabolic pathways in ILCs to identify the cell-intrinsic mechanisms and checkpoints that regulate appropriate ILC activity.

The student will receive excellent training in translational immunology within the Manchester Collaborative Centre for Inflammation Research (MCCIR), in which GlaxoSmithKline (GSK) are active partners. The Hepworth lab will provide expertise in ILC biology and inflammatory diseases and will be supported by the Travis lab's extensive experience in immune regulation and established clinical links to study the immunology of human inflammatory disease. The industrial partner (GSK) will aid in elucidating novel mechanisms through which ILCs regulate inflammation and to increase understanding of how ILC function is altered upon perturbation of pathways that are the focus of current and future therapeutic strategies. GSK will provide critical input, training and resources that will foster rapid development of basic research findings to maximise translation into the clinic.