"ILC2 development and function"

Andrew McKenzie

Medical Research Council (MRC) Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK

Andrew McKenzie's research investigates how the innate immune system and adaptive immune system protect the body from infection, but can also lead to inflammation and pathology. He has defined and characterised how biological networks orchestrate responses to pathogens and how dysregulation of these biological pathways can lead to diseases such as asthma and allergy. His identification of the cytokine Interleukin 13 and the subsequent unearthing of its central role in allergic asthma led to his discovery of type-2 innate lymphoid cells (ILC2). These cells secrete large quantities of cytokines and represent a new druggable biological target for intervention in inflammation and infection. McKenzie was elected a Fellow of the Royal Society (FRS) in 2017 and a Fellow of the Academy of Medical Sciences (FMedSci) in 2011. Regulation of the immune system is fundamental to protecting the host from infection whilst constraining autoimmunity, undesirable inflammation and immunopathology. Immune dysregulation can lead to diseases such as asthma and allergy (Figure 1), autoimmunity and leukaemia. Using techniques including mouse genetics, fluorescence imaging and gene expression analysis we discovered group 2 innate lymphoid cells (ILC2s) as significant new participants in immune regulation through their cytokine secretion (Figure 2). We now know that ILC2s belong to a larger family of ILCs that develop from lymphoid precursors that also give rise to the T and B cell lineages. We aim to identify the transcriptional pathways that regulate this differentiation and gain molecular insight into cell commitment. ILC2s localise predominantly at mucosal surfaces where they act as critical sentinels for tissue damage and infection, at the interface of innate and adaptive immunity. Our goal is to determine the cellular and molecular pathways that regulate ILCs during homeostasis and disease, and how they might be targeted therapeutically in humans.