OBJECTIVE: To clarify the significance of immunometabolism in systemic lupus 
erythematosus (SLE), and to determine the effect of calcium/calmodulin-dependent 
protein kinase 4 (CaMK4) on T cell metabolism.
METHODS: Metabolomic profiling was performed using capillary electrophoresis 
mass spectrometry in naive T cells from MRL/lpr mice treated with anti-CD3/CD28 
antibodies in the absence or presence of a CaMK4 inhibitor (KN-93). The 
expression of GLUT1 and CaMK4 in CD4+ T cells from healthy controls (n = 16), 
patients with inactive SLE (n = 13), and patients with active SLE (n = 14) was 
examined by flow cytometry and quantitative polymerase chain reaction. In vitro 
experiments were performed to determine the effect of KN-93 on the expression of 
GLUT1 during Th17 cell differentiation in T cells from patients with SLE.
RESULTS: CaMK4 inhibition significantly decreased the levels of glycolytic 
intermediates such as glucose-6-phosphate, fructose-6-phosphate, 
fructose-1,6-diphosphate, pyruvate, and lactate (P < 0.05), whereas it did not 
affect the levels of the pentose phosphate pathway intermediates such as 
6-phospho-d-gluconate, ribulose-5-phosphate, ribose-5-phosphate, and 
phosphoribosyl pyrophosphate. The expression levels of GLUT1 and CaMK4 in 
effector memory CD4+ T cells were significantly higher in patients with active 
SLE compared to healthy controls (P < 0.01 and P < 0.05, respectively) and 
patients with inactive SLE (P < 0.05 and P < 0.01, respectively). A functional 
analysis revealed that CaMK4 inhibition decreased the expression of GLUT1 during 
Th17 cell differentiation (P < 0.01), followed by a reduction of interleukin-17 
(IL-17) production (P < 0.05).
CONCLUSION: The results of the study indicate that the activity of CaMK4 could 
be responsible for glycolysis, which contributes to the production of IL-17, and 
CaMK4 may contribute to aberrant expression of GLUT1 in T cells from patients 
with active SLE.