Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells
|SPEAKER:||Laurence Morel, PhD, Mary and Bryan Whisenant Professor of Pathology, University of Florida Health|
Aug 28, 2019
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4+ T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programs. Patients with SLE as well as lupus-prone mice present with activated immune metabolism, mostly characterized in CD4+ T cells. Treatments with specific metabolic inhibitors to normalize these features has shown therapeutic effects.
In this webinar, we will discuss the metabolism of a specific type of effector CD4+ T cells, the follicular helper T (TFH) cells, which are expanded in SLE where they are required to produce high affinity autoantibodies. Using a combination of microarray and NanoString’s nCounter® analyses (RUO), we show that autoimmune TFH cells and exogenous antigen-specific TFH cells have unique gene expression signatures, including a solute transporter gene signature showing a different glucose and amino acid flux between the two TFH cell types. Similar analyses should be conducted on the specific metabolic requirements of other immune cell subsets associated with SLE to investigate whether they represent potential therapeutic targets for metabolic inhibitors.
FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.