Defining the metabolic signatures of tissue resident Innate Lymphoid Cells

Innate Lymphoid Cells (ILCs) is a recently discovered family of tissue resident lymphocytes capable of rapid responses to a broad range of inflammatory cues. Whilst present at low numbers in circulation, ILCs acquire a more activated phenotype in tissues.

Adaptations to the local tissue microenvironment such as in a tumor, can also further influence and alter ILC functionality.

However, the key factors and metabolic pathways linking activation to tissue adaptation in human ILCs remain poorly understood.

We will examine the metabolic profiles of ILCs obtained from a wide range of non-diseased human tissues including spleen, lung, liver, ileum and colon using the latest metabolomics and single-cell transcriptomics and epigenetics techniques. Comparative studies will be done on ILCs from inflamed and cancerous intestinal tissues.

Defined as key regulators of activation and differentiation in other lymphocytes, we will further determine how PPAR-γ and BHLHE40 shape human ILC metabolism and tissue adaptions.

Finally, we will seek to determine how checkpoint therapies such as anti-PD-1 influence ILC function in a murine model of cancer.

Our results will provide a greater understanding of which metabolic pathways shape ILC function in different human tissue sites and define important pathways that are altered upon inflammation and cancer in the intestines. The findings will impact on the efficacy of both current and novel anit-tumor  therapeutics.