Immunometabolism & Inflammation Lab

Pathophysiology and Therapy of Immune and Inflammatory Diseases
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

Our group is interested in understanding how chronic inflammation may accelerate the aging process. Specifically, we want to study how immune cell metabolism may act as a therapeutic target in delaying aging and age-associated diseases.

The activation, expansion, differentiation and the regression to homeostasis of immune cells are processes associated with metabolic changes. Following antigen recognition, T cells are activated and initiate a proliferation phase characterized by a metabolic change similar to the Warburg effect described in tumoral cells. This metabolic reprogramming could be advantageous for cells that proliferate rapidly, such as cancerous or immune cells. T-cell differentiation and functional fate could be altered by modulating its metabolism. These results have opened up a new field of research, known as immunometabolism, that studies metabolic regulation in the immune response and is currently considered a promising therapeutic window in cancer and autoimmune disease research.

Our major scientific interest involves studying the role of metabolic regulation in the inflammatory response, and defining how immunometabolism may be used as a therapeutic tool in inflammatory diseases and pathologies associated with aging. To do this, we used a murine model whose Tfam gene is specifically deleted in T-cells. Tfam depletion induces a severe decrease in the amount of mitochondrial DNA in T lymphocytes and collapses the expression of important components within the electron transport chain provoking severe mitochondrial dysfunction, alteration of oxidative phosphorylation (OXPHOS) and a significant decrease in mitochondrial ATP production.

The Tfam mouse model has helped us to identify the role of mitochondrial metabolism in the regulation of T-cell inflammatory response by controlling lysosome function. This novel relationship between mitochondria and the cell degradation system can be exploited as a possible therapeutic window in halting chronic inflammation and preventing human diseases associated with aging.

In summary, our lab uses a multidisciplinary approach to explore immunometabolism as a new therapeutic target against chronic inflammation and aging. We hope this strategy strengthens our understanding and helps us learn about new molecular mechanisms involved in human inflammatory pathologies to improve clinical interventions in age-associated diseases.

Immunometabolism & Inflammation Lab

Biomolecules & Cell D.
Molecular Biomedicine
María Mittelbrunn