(A) Immunoblot analysis of murine GLUT3, ACLY, IRF4, NFATc1 and GAPDH expression. (B) Analysis of Slc2a3 (GLUT3) gene expression in naïve CD4+ T cells and T helper (Th) cell subsets by qRT-PCR; means ± SEM of 5-6 mice. (C and D) Glycolytic proton efflux rate (glycoPER) analyses of WT and GLUT3-deficient Th1 (C) and Th17 (D) cells using a Seahorse extracellular flux analyzer; means ± SEM of 5 mice. (E) Proliferation analysis of WT and GLUT3-deficient Th1 and Th17 cells. (F-H) Flow cytometric analysis of IFNγ
(G) and IL-17 (H) production of WT and GLUT3-deficient Th1, Th17 and pathogenic Th17 (pTh17) cells after re-stimulation with PMA/Iono for 5 h; means ± SEM of 9-15 mice. (I) Generation of mixed BM chimeras using BM from CD45.2+
Slc2a3fl/flCd4Cre and CD45.1+ WT mice at a 1:1 ratio. 8 weeks after reconstitution, the production of IFNγ and IL-17 in CD4+ T cells of WT and GLUT3-deficient BM origin was analyzed; means ± SEM of 6 mice. (J-L) Ectopic expression of GLUT3 in T cells augments Th17 cell effector function. (J) Retroviral transduction of WT T cells with GLUT3 or empty control vectors (EV). Immunoblot analysis of GLUT3 overexpression. (K) Flow cytometric analysis of IFNγ and IL-17 production of GLUT3-transduced Th1 and Th17 cells; means ± SEM of 5-8 mice. (L) Clinical EAE scoring of Rag1−/− mice after transfer of GLUT3-transduced 2D2 T cells; means ± SEM of 4 mice per cohort. **, p<0.01, ***, p<0.001 by unpaired Student’s t-test (B), (G-I) and (K); n.s., non-significant.