Fig. 1

ART suppresses Th17 response via inhibiting glycolysis and ameliorates Sjog̈ren’s syndrome development. a ESS mice were induced and treated with vehicle or ART. Saliva flow rates were measured (n = 10). b The levels of anti-SSA IgG in serum were measured by ELISA (n = 10). c Representative flow cytometric profiles showing Th17 cells in draining cervical lymph nodes were presented. The numbers of Th17 cells were enumerated (n = 8–9). d Representative H&E staining images of SG tissues were shown. Histological scores were analyzed (n = 9). e Representative confocal images showing T cells infiltration in SGs were presented. f The schematic diagram shows the generation of humanized SS mice and ART treatment. g Saliva flow rates were measured on day 28 after cell transfer (n = 6). h Representative H&E staining images of SG tissues were shown. Histological scores were analyzed. i Representative confocal images showing infiltrating human Th17 cells (arrows) in SG. j Human Th17 cells in spleen (SP) and SG were analyzed by flow cytometry (n = 6). k T-SNE visualization of CD4 T cells from PBMC of healthy controls (HC) and pSS patients. l GSEA plots showing an enrichment of glycolytic signatures in Th17 from pSS patients compared with those from HC. m–o Purified CD4 T cells from healthy control (HC) and pSS patients were cultured under Th17 polarization conditions and treated with vehicle or ART. CD4 T cells without stimulation were collected as resting cells. The expression levels of Glut1 were detected by flow cytometry (m and o, n = 3). The cultured Th17 cells were incubated with 2-NBDG solution for glucose uptake assay. The fluorescence intensities were analyzed by flow cytometry (n–o, n = 4–5). p The cultured Th17 cells from HC and pSS patients were treated with vehicle or ART and collected for seahorse glycolysis stress test. ECAR values were monitored with sequential addition of glucose, oligomycin, and 2-deoxy-glucose (2-DG). The ECAR values representing glycolysis were calculated and analyzed (n = 3–5). q Schematic figure illustrates that ART increases proteasomal degradation of IRF4 and suppresses glycolysis in Th17 cells. f Includes modified images from Servier Medical Art (http://www.servier.com). Data were obtained from at least three independent experiments and presented as mean ± SD; one-way ANOVA (a–d, o–p) and paired t-test (g, h, j); *P < 0.05; **P < 0.01; ***P < 0.001