Dimethyl Fumarate Regulates Treg–Th17 Axis in Psoriasis

psoriasis on elbow
psoriasis on elbow
The effects of DMF—both in vivo and in vitro—on T cells, which play a key role in the pathogenesis of psoriasis, were examined.

Dimethyl fumarate (DMF) enhances the ratio of T regulatory (Treg) cells to T helper (Th)17 lineage cells in patients with psoriasis which is a new mechanism of action for DMF, according to study research published in the British Journal of Dermatology.

Researchers sought to analyze the effects of DMF in patients with psoriasis and in vitro on T cells, which are involved in the pathogenesis of psoriasis. The study included 16 untreated patients with psoriasis, 27 patients treated with DMF (mean dose, 559.15 mg per day), and a third group of 10 patients who were examined before and after DMF treatment.

In the patients who received DMF, the investigators found an increase in the frequency of Treg cells and a decrease in Th17 lineage cells. In addition, T cells cultured in vitro with DMF demonstrated a reduced viability and inhibition of activation and proliferation in response to stimulation due to the oxidative effects of DMF. “Treg cells exhibited an increased ability to resist the oxidative stress induced by DMF in vitro,” stated the study authors. “This is a new mechanism of action for DMF.”

The selective reduction of Th17 cells without a reduction in Th1 cells or Treg cells explains the efficacy of DMF in psoriasis, according to the researchers. “Given the importance of the IL-17 pathway in psoriasis, as demonstrated by the success of anti–IL-17 therapy, this finding has important clinical relevance and suggests that the beneficial effect of DMF may be mediated at least in part via inhibition of Th17 cells, or by IL-17 directly,” they stated.

Disclosures: Some study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Sulaimani J, Cluxton D, Clowry J, et al. Dimethyl fumarate modulates the Treg–Th17 cell axis in patients with psoriasis [e-pub ahead of print]. Br J Dermatol. doi: 10.1111/bjd.19229