Compared to grafts from mice receiving WT Tregs, hearts still beating at 100 days after transplantation in mice receiving Sirt32/2 Tregs had increased inflammation, fibrosis, and T cell infiltration.
Immunometabolism
Understanding the pathways important to ATP generation in immune cells in the tumor microenvironment is a burgeoning area of research that may offer new perspectives for anti-cancer therapy. Similarly, understanding how tumors resist or evade immune destruction may entail consideration of the effects of lactate and other tumor products on the metabolic functions of immune cells. Dr. Ulf Beier is heading research in this nascent field of immunometabolism, with a particular focus on pathways active in Tregs vs. effector T cells.
The Treg transcription factor Foxp3 controls metabolic adaptations including a downregulation of Myc and glycolysis, an induction of oxidative phosphorylation, and an increased NAD:NADH ratio. These metabolic changes allow Tregs to thrive in low-glucose, high-lactate environments, thus maintaining their immunosuppressive function under metabolically challenging conditions.
Selected Publications
Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments. Angelin A, Gil-de-Gómez L, Dahiya S, Jiao J, Guo L, Levine MH, Wang Z, Quinn WJ 3rd, Kopinski PK, Wang L, Akimova T, Liu Y, Bhatti TR, Han R, Laskin BL, Baur JA, Blair IA, Wallace DC, Hancock WW, Beier UH. Cell Metab. 2017 Jun 6;25(6):1282-1293.
Essential role of mitochondrial energy metabolism in Foxp3⁺ T-regulatory cell function and allograft survival. Beier UH, Angelin A, Akimova T, Wang L, Liu Y, Xiao H, Koike MA, Hancock SA, Bhatti TR, Han R, Jiao J, Veasey SC, Sims CA, Baur JA, Wallace DC, Hancock WW. FASEB J. 2015 Jun;29(6):2315-26.
