Post doc trainee Feinstein Institutes for Medical Research Manhasset, New York, United States
Abstract Text: The generation and function of T follicular helper (Tfh) cells is critical for protective immune responses against foreign antigens, but uncontrolled generation and altered functionality of Tfh cells appears to be critically involved in the development of some autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). Although increased metabolism in total CD4+ T cells has been described in lupus, the metabolic profile of Tfh cells is not described. We characterized glycolysis/TCA in Tfh subsets and investigate whether intervention of metabolism regulates function of Tfh cells from SLE. We analyzed glucose uptake, lactate, mitochondrial mass and mitochondrial membrane potential in CD4+ T, Tfh (CXCR5+), Tfh1, Tfh2 and Tfh17 cells purified from peripheral blood of SLE patients comparing them to healthy controls. Increased glucose uptake by stimulation in total SLE CD4+ T cells, but was not in Tfh subsets. No difference in the level of lactate in Tfh subsets. Different to CD4+ T cells, Tfh cells do not display increased glycolysis. However, Tfh17 cells have an increased mitochondrial activation which is depending on glucose as a fuel source. Blockage of glycolysis and TCA by STF-31 and IACS-10759, Tfh cells activation (CD69+) and costimulatory molecules ICOS and PD1 were down-regulated. Analyzing in vitro B cell activation by Tfh17, there was not difference in the plasmablast differentiation and Ig secretion by PB cells in Tfh17 SLE treated with inhibitors. Thus, this study elucidates the importance of metabolism reprograming that T cells exerts on effector T cells through modulation of glycolysis and TCA cycle.
