Fig. 1.

S1P₁ in CNS cell lineages is critical for FTY720 efficacy. (A) Mean clinical score of WT EAE mice challenged with FTY720 daily treatment (1, 3, and 10 mg/kg; n = 5 for each dose of FTY720) compared with saline control (n = 6). (B) Reduction of PBLs by FTY720 at 24 h [percentage at 24 h relative to time = 0; 3 mg/kg FTY720 exposure obtained from animals in A (n = 4 of each group)]. (C) Mean clinical score of EAE induced in CNS S1P₁ conditional null mutants [S1pr1^loxP/loxP; Nestin-Cre; with FTY720 (n = 9) and without FTY720 (n = 9)] compared with littermate controls [S1pr1^loxP/loxP; with FTY720 (n = 7) and without FTY720 (n = 8); daily administration of 3 mg/kg FTY720]. (D) Reduction of PBLs by FTY720 at 24 h [percentage at 24 h relative to time = 0; 3 mg/kg FTY720 exposure obtained from animals in C (n = 3 for each group)]. (E) Mean clinical score of EAE induced in neuronal S1P₁ conditional null mutants (S1pr1^loxP/loxP; synapsin-cre; n = 12) compared with littermate controls (n = 7; daily administration of 3 mg/kg FTY720). (F) Reduction of PBLs by FTY720 at 24 h [percentage at 24 h relative to time = 0; 3 mg/kg FTY720 exposure obtained from animals in E (n = 6 for each group)]. (G) Mean clinical score of EAE induced in astrocyte S1P₁ conditional null mutants (S1pr1^loxP/loxP; GFAP-Cre; n = 12) compared with littermate controls (n = 27; daily administration of 3 mg/kg FTY720). (H) Reduction of PBLs by FTY720 at 24 h [percentage at 24 h relative to time = 0; 3 mg/kg FTY720 exposure obtained from animals in G (n = 4 or n = 3 for control or conditional mutant mice)]. Data in all figures are represented as mean ± SEM. ▽ and ▼ indicate the start and stop of FTY720 administration, respectively. Actual values for peripheral blood lymphocytes for B, D, F, and H were documented (Table S1). Clinical scores of A, C, E, and G were statistically analyzed using Mann–Whitney's test (Tables S2–S5).