Aleksandra Dyczko – VIB Laboratory of Translational Immunomodulation Center for Inflammation Research, Hasselt University; Ibrahim Hamad – VIB Laboratory of Translational Immunomodulation Center for Inflammation Research, Hasselt University
Prof VIB Laboratory of Translational Immunomodulation Center for Inflammation Research, Hasselt University Hasselt, Limburg, Belgium
Abstract Text: FOXP3+ regulatory T cells (Tregs) are central for maintaining peripheral tolerance and play a critical role in promoting immune homeostasis and tissue regeneration. Depending on the environment, they are able to suppress pro-inflammatory responses by different mechanisms, such as cell contact dependent mechanism or by secretion of anti-inflammatory cytokines. Tregs have distinct metabolic needs and preferentially rely on mitochondrial metabolism to exert their suppressive function. We have recently shown that changes in the ionic microenvironment and increased Na+ could inhibit mitochondrial respiration of Tregs through interference with the electron transport chain (ETC), leading to the acquisition of a pro-inflammatory Th1-like phenotype mimicking dysfunctional Tregs frequently observed in autoimmunity. Interestingly, mitochondrial Na+ accumulation and up-regulation of Na+/Ca2+ exchanger activity dependent blockade of the ETC has been previously described also under isotonic hypoxic conditions. We therefore investigated by various immunological and metabolic assays the effects of hypoxia on Treg immunometabolism and functionality. Of note, temporary hypoxia induced substantial changes in human Treg immunometabolism and a phenotype closely mimicking dysfunctional pro-inflammatory Th1-like Tregs. Thus, the interference with this pathway could potentially serve as a novel target to manipulate or restore Treg function under oxygen-deprived conditions, having important implications for various diseases.
