Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions
Fig 2
Sodium lactate and lactic acid act on CD4+ and CD8+ T cell subsets, respectively, through specific cell membrane transporters.
(A) Total protein levels of the transporters Slc16a1 and Slc5a12 as assessed by western blot in activated CD4+ and CD8+ T cell subsets. (B–D) In vitro chemotaxis (4 h time point) of activated CD8+ T cells towards CXCL10 (300 ng/ml) in the presence of lactic acid (10 mM) alone, or in combination with α-cyano-4-hydroxycinnamate (CHC) (425 μM), phloretin (25 μM), or anti-Slc16a1 antibody (2.5 μg/ml) (B), or increasing concentrations of AR-C155858 as indicated in the figure (C), and activated CD4+ T cells towards CXCL10 (300 ng/ml) in the presence of sodium lactate (10 mM) alone, or in combination with an anti-Slc5a12 antibody (2.5 μg/ml) or two specific short hairpin RNAs (shRNAs) (D). An isotype control antibody has been included to control for antibody specificity (B, D), and a nonspecific shRNA has been included to control for gene knockdown specificity (D). (B–D) n = 3. Underlying numerical data and statistical analysis can be found in the supporting file, S1 Data, Fig 2B–2D. Values denote mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001.