Researchers at Turku Bioscience in joint collaboration with the Örebro University, Sweden have uncovered new ‘metabolic signatures’ of human CD4+ T-cells
From left to right: Dr. Alex M Dickens*, Dr. Partho Sen*, Dr. Syed Bilal Ahmad Andrabi+ and Dr. Tanja Buchacher+. ‘*’ represents Systems Medicine group headed by Prof. Matej Orešič, and ‘+’ represents Molecular Systems Immunology group headed by Prof. Riitta Lahesmaa.
T-cells are white blood cells that coordinate our immune response and provide protection against pathogens and cancer. Abnormally functioning T cells may lead to the development of cancer or autoimmune disorders.
Scientists at University of Turku and Örebro University studied metabolism of human T cells with sophisticated, cutting edge technologies such as computer-based modelling, high throughput lipidomics, transcriptomics techniques, and conducting in vitro knockdown experiments. They identified that certain molecular lipids such as ceramides and glycosphingolipids play an important role in the functioning of human T cells.
Intriguingly, these lipids were found to be regulated differently in T cell subsets. Experimental manipulation of glycosphingolipid pathways altered the T-cell functions. Particularly, the expression of proinflammatory cytokines was affected in a subset of T-cells called Th17 cells, known to be associated with various immune-mediated disease such as autoimmune diseases, and cancer. In particular, the study identified serine palmitoyl transferase (SPT), as an important target for regulating the expression of proinflammatory cytokine (IL17A and IL17F) by Th17 cells. The authors say “ Our results provide basis for engineering and manipulating metabolism of human T-cells to treat immune-mediated diseases”.
Manipulating human T-cell metabolism to modulate their early specification for therapeutic purposes is a new paradigm and offers significant new options in the future to develop safe and effective therapies for cancer and autoimmune diseases. Since ceramides are lipotoxic lipids that are commonly elevated in obesity and insulin resistance, our study may also offer clues about the poorly understood overlap in co-morbidities between specific immune-mediated diseases characterized by expression of proinflammatory cytokines and metabolic diseases, such as has been found to occur in COVID19.
Article published in Cell Reports, titled as “Quantitative genome-scale metabolic modeling of human CD4+ T-cell differentiation reveals subset-specific regulation of glycosphingolipid pathways”. Link to article