The immune system is crucial for a health body function and protects us from severe infection. However, a dysregulated immunity can cause inflammation, autoimmune diseases and cancer. Especially, the control of immune cell metabolism as emerged as a powerful way to regulate immunity.
The Brenner Lab investigates the metabolic regulation of the immune system and how this ensures a coordinated immune response and homeostasis. We seek to define the molecular, metabolic and cellular processes of inflammation and integrate in vitro with in vivo studies to gain a comprehensive picture of inflammation and cancer.
Figure 1. Schematic diagram of energy-generating metabolic pathways and their regulators.
Kurniawan H, Soriano-Baguet L, Brenner D (submitted).
It has become clear that the metabolic reprogramming that occurs in activated immune cells is essential for their proper functions leading to the creation of a new field of research termed “immunometabolism”.
Recent studies have underlined the role of cellular metabolism in the generation and maintenance of various types of immune cells. In T cells for example, distinct subsets utilize different energetic and biosynthetic pathways to sustain their activities. Naive CD4+ Th cells use oxidative phosphorylation (OXPHOS) for energy generation when in the quiescent state. Upon activation by antigen, these cells proliferate and differentiate into CD4+ T helper (Th) effector cells (Teffs), such as Th1, Th2, and/or Th17 cells and switch from OXPHOS to a highly glycolytic form of metabolism. In contrast, upon activation, regulatory T cells (Tregs) employ glycolysis at a low rate and high lipid oxidation. This divergent use of metabolic pathways can influence cell fate in various ways. For instance, fatty acid oxidation (FAO) fosters the generation of Tregs while dampening the polarization of Teffs.
Our lab therefore focus on investigating how cellular metabolism affects cellular functions in specific contexts and various inflammatory diseases. Our analyses are not only focused on T cells, but also include innate immune cells and B cells. A key goal and focus of all our projects is to identify the metabolic checkpoints that interfere with cellular activity in the context of abnormal immune homeostasis like inflammation and cancer.