Mitochondrial metabolism: Deciphering new routes to control T cell function

Metabolism plays a critical role in immune cell differentiation, activation, and plasticity. Adjustments in cellular metabolism are often associated with epigenetic changes and alteration of transcriptional programs. This determines the adaptation of immune cells to the respective environment and to their functional state, which in turn ensures a productive immune response. T cells are an integral part of the immune system. Recently, our lab significantly contributed to the understanding how metabolism controls T cell-based immunity (Kurniawan et al. 2020; Mak and Grusdat et al. 2017). The control of T cell metabolism offers a great opportunity to intervene therapeutically with the function of these important immune cells and thus to mitigate detrimental inflammatory diseases including autoimmunity and cancer. A central metabolic regulatory node are the mitochondria. However, our understanding of how mitochondrial metabolism controls T cell function and how it affects different T cell subsets is still incomplete. In this project, we will study mitochondrial metabolism in T cells. We will focus on the manipulation of mitochondrial metabolism with the ultimate aim of obtaining insights into the functional properties of T cells. We will investigate this using genetic altered mouse mutant models in combination with in vivo disease models for autoimmunity and infection and with studies on human T cells. We will conduct a detailed molecular, metabolic and cellular analysis of mitochondrial T cell metabolism that also includes transcriptional, metabolic and epigenetic profiling. The overall aim is to characterize novel metabolic checkpoints in T cells that are of disease relevance.