Background/Purpose: Activated T cells make a significant contribution to inflammation in systemic lupus erythematosus (SLE). We know that cellular metabolism regulates the activation of T cells. Evidence from patients with multiple sclerosis indicates that dimethyl fumarate (DMF), an electrophile, targets cellular metabolism to modulate CD4+T cell activation and function.

Here, we investigated whether DMF modulates T cell metabolism and function in samples from patients with SLE in a series of in vitro experiments.

Methods: All experiments were performed using isolated T cells from freshly drawn whole blood samples from patients with SLE. T cells were isolated using negative selection using Stem cell or Miltenyei magnetic bead separation kit. Isolated T cells were activated with anti-CD3 and IL-2 and incubated with either DMF at 25μM concentration or DMSO alone for three or seven days at 37°C and 5% CO₂ before harvesting.

Results: In Seahorse experiments, after three days of incubation dimethyl fumarate (DMF) inhibited Figure A-i) the oxygen consumption rate (OCR) and A-ii) extra cellular acidification rate (ECAR) in isolated T cells when compared with samples incubated with vehicle, dimethyl sulfoxide (DMSO). Our results revealed that DMF significantly inhibited: 1) aerobic glycolysis and oxidative phosphorylation in activated T cells from patients with SLE (n=4) (Figure A- i and ii), in vitro; 2) T cell activation and proliferation as assessed by a reduction in the frequency of CD69 (n=4) and D) Ki67 (n=2) positivity, respectively (Figure B-E); 3) Collectively, these results suggest that DMF inhibits T cell activation and proliferation in samples from patients with SLE.

After 7 days of incubation, DMF significantly inhibited the expression of activating NK receptors CD158a and NKG2D on T cells whereas there was a trend toward enhancing the expression of inhibitory NK receptors NKG2A and CD158b (Figure F-I).

After 7 days of incubation, DMF significantly reduced intracellular expression of IFN-γ, TNF-α, IL-17 and secretion of pro-inflammatory cytokines IFN-γ and TNF-α in supernatants (Figure J – N).

Conclusion: Our preliminary data indicated that DMF modulates metabolic programming to inhibit activation, proliferation, and secretion of proinflammatory cytokines from T cells patients with SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dimethyl-fumarate-modulates-t-cell-metabolism-and-function-in-systemic-lupus-erythematosus-patient-samples/