Editors' ChoiceImmunology

Normalizing immune cell metabolism treats lupus

Sci. Signal.  17 Feb 2015:
Vol. 8, Issue 364, pp. ec37
DOI: 10.1126/scisignal.aaa9098

Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system attacks normal, healthy tissues. CD4+ T cells are critical to SLE pathogenesis, but it has remained unclear if metabolism in these cells contributes to disease. Now, Yin et al. report that two metabolic pathways—glycolysis and mitochondrial oxidative metabolism—are elevated in cells from SLE patients as well as in mouse models of disease. What’s more, inhibitors of these pathways currently in the clinic—2-deoxy-D-glucose and metformin—normalized T cell metabolism and decreased markers of SLE in animal models as well as in cells from SLE patients. These data suggest that inhibiting both glycolysis and mitochondrial metabolism could be a new therapeutic strategy for treating SLE.

Y. Yin, S.-C. Choi, Z. Xu, D. J. Perry, H. Seay, B. P. Croker, E. S. Sobel, T. M. Brusko, L. Morel, Normalization of CD4+ T cell metabolism reverses lupus. Sci. Transl. Med. 7, 274ra18 (2015). [Abstract]

M. M. Mehta, N. S. Chandel, Targeting metabolism for lupus therapy. Sci. Transl. Med. 7, 274fs5 (2015). [Abstract]