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Dimethyl fumarate modulates the Treg-Th17 cell axis in patients with psoriasis
J Sulaimani1, D Cluxton1, J Clowry2
1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Background:
Dimethyl fumarate (DMF) is the active ingredient of Skilarence™ and Tecfidera™, which are used for the treatment of psoriasis and multiple sclerosis, respectively. Various immunomodulatory mechanisms of action have been identified for DMF; however, it is still unclear what effects DMF exerts in vivo in patients with psoriasis.
Objectives:
In this study we examined the effects of DMF, both in vivo and in vitro, on T cells, which play a key role in the pathogenesis of psoriasis.
Methods:
The frequency of T-cell subsets was examined by flow cytometry in untreated patients with psoriasis or those treated with DMF. The effects of DMF in vitro on T-cell survival, activation and proliferation, and cell-surface thiols were assessed by flow cytometry.
Results:
In patients with psoriasis treated with DMF we observed an increase in the frequency of T regulatory (Treg) cells and a decrease in T helper (Th)17 lineage cells and the associated cytokines interleukin-17, interleukin-22 and granulocyte-macrophage colony-stimulating factor. T cells cultured in vitro with DMF exhibited reduced viability, and inhibition of activation and proliferation in response to stimulation due to the oxidative effects of DMF. However, the frequency of Treg cells increased in the presence of DMF due to their heightened ability to resist DMF-induced oxidative stress.
Conclusions:
DMF enhanced the ratio of Treg cells to Th17 cells in patients with psoriasis, in patients with multiple sclerosis and in vitro. Furthermore, our data suggest that this is at least in part as a result of the differential effects of DMF on Treg cells compared with conventional T cells.
Insights
Dimethyl fumarate (DMF) increases regulatory T cells (Treg) and decreases T helper 17 (Th17) cells in psoriasis patients. This shift in T cell balance is key to DMF
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Dimethyl fumarate (DMF) is a therapeutic agent used for psoriasis and multiple sclerosis.
- The precise in vivo effects of DMF on T cells in psoriasis patients remain incompletely understood.
- T cells are critically involved in the pathogenesis of psoriasis.
Purpose of the Study:
- To investigate the in vivo and in vitro effects of DMF on T cells in the context of psoriasis.
- To elucidate the impact of DMF on T cell subsets, activation, proliferation, and survival.
- To understand the differential effects of DMF on regulatory T cells (Treg) versus T helper 17 (Th17) cells.
Main Methods:
- Flow cytometry was employed to analyze T cell subset frequencies in patients with psoriasis.
- T cells were cultured in vitro with DMF to assess viability, activation, proliferation, and cell-surface thiols.
- Analysis included untreated psoriasis patients and those undergoing DMF treatment.
Main Results:
- DMF treatment in psoriasis patients led to an increased frequency of Treg cells and a decreased frequency of Th17 cells.
- In vitro studies showed DMF reduced T cell viability, activation, and proliferation due to oxidative stress.
- Treg cells demonstrated increased resistance to DMF-induced oxidative stress, leading to their relative enrichment.
Conclusions:
- DMF treatment enhances the Treg to Th17 cell ratio in psoriasis patients, both in vivo and in vitro.
- This immunomodulatory effect is partly attributed to DMF's differential impact on Treg cells compared to conventional T cells.
- DMF's ability to modulate T cell populations offers insights into its therapeutic mechanisms for psoriasis.
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