Targeting inflammatory TH17 cells can effectively treat autoimmune diseases, but existing approaches also inhibit homeostatic TH17 cells, thereby increasing the risk of infection. Here, Wu et al. report that inflammatory TH17 cells in the spinal cord of EAE mice express higher levels of glycolysis pathway genes than commensal bacteria-induced homeostatic TH17 cells. Specific knockout of glucose phosphate isomerase selectively eliminated inflammatory TH17 cells. Unlike homeostatic TH17 cells, inflammatory TH17 cells could not compensate by pentose phosphate pathway flux and increased mitochondrial respiration, owing to their hypoxic environment.
Nature Reviews Drug Discovery 19, 512 (2020)