Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions
Fig 5
High Slc5a12 expression in RA in humans.
(A) Representative images of RA synovial tissues stained for CD3 displaying progressively higher degree of T cell infiltration as quantified using a semiquantitative score from T0 (absence of infiltrating T-cells) to T3 (large number of infiltrating T cells organizing in ectopic follicles) as shown in [35]. (B) Relative mRNA expression levels of Slc16a1 and Slc5a12 in the synovial fluid isolated from the joints of RA patients. Samples are grouped based on their T cell score as described in A. Values denote mean ± SD, (T0) n = 6 and (T2–3) n = 7. *p < 0.05. (C) Double immunofluorescence staining for Slc5a12 and CD4 or CD8 in the synovial tissue of RA patients. Slc5a12 (green) is highly expressed within the RA synovia in the presence of a high degree of CD4+ (red) T cell infiltration. Merging (yellow) of the green and red channels demonstrates that Slc5a12 is selectively expressed by CD4+ but not CD8+ infiltrating T cells. Quantification of the % double positive cells is provided upon counting positive cells (single and double positive for each marker) in at least 6 images per condition. Columns represent % of double positive CD4+ Slc5a12+ population within the CD4+ or Slc5a12+ cells and % of double positive CD8+ Slc5a12+ population within the CD8+ or Slc5a12+ cells. Scale bars: 50 μm. (D) In vitro chemotaxis (4 h time point) of activated human CD4+ and CD8+ T cells towards CXCL10 (300 ng/ml) in the presence of lactic acid (10 mM) or sodium lactate (10 mM). (E) Intracellular staining of IL-17A in activated human CD4+ T cells treated with sodium lactate (10 mM) or left untreated. (D) n = 3. (E) n = 4. (B–E) Underlying numerical data and statistical analysis can be found in the supporting file, S1 Data, Fig 5B–5E. Values denote mean ± SD. *p < 0.05.