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Updated: May 28, 2026
09:51
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells
Kamran Ghoreschi1, Jürgen Brück, Christina Kellerer
1Department of Dermatology, University Medical Center and 2 Interfaculty Institute for Biochemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
The Journal of Experimental Medicine
|October 12, 2011
Summary
Fumarates treat autoimmune diseases like multiple sclerosis (MS) and psoriasis by reprogramming immune cells. This approach generates specific dendritic cells (DCs) that reduce key inflammatory signals, offering a novel therapeutic strategy.
Area of Science:
- Immunology
- Pharmacology
- Dermatology
Background:
- Interleukin-12 (IL-12) and Interleukin-23 (IL-23) drive pathogenic T helper cell differentiation in multiple sclerosis (MS) and psoriasis.
- Despite shared drivers, MS and psoriasis exhibit distinct responses to existing therapies.
Purpose of the Study:
- To investigate the mechanism by which fumarates exert therapeutic effects in autoimmune diseases.
- To explore the role of fumarate treatment in modulating immune cell function and cytokine production.
Main Methods:
- Human and mouse models of autoimmune diseases were used.
- Fumarate treatment effects on T helper cell differentiation and dendritic cell (DC) function were analyzed.
- Mechanisms involving glutathione (GSH) depletion, hemoxygenase-1 (HO-1) expression, and STAT1 phosphorylation were investigated.
Main Results:
- Fumarate treatment induced IL-4-producing Th2 cells and type II DCs in humans and mice.
- Type II DCs produced IL-10 and suppressed IL-12 and IL-23 production.
- Fumarate-induced GSH depletion led to HO-1 expression and impaired STAT1 phosphorylation, inhibiting IL-23p19 and IL-12p35 transcription respectively.
Conclusions:
- Fumarates induce type II DCs via GSH depletion, HO-1 expression, and STAT1 inactivation.
- This mechanism ameliorates Th1- and Th17-mediated autoimmune diseases like MS and psoriasis by reducing IL-12 and IL-23 production.
- Fumarates represent a promising therapeutic strategy for inflammatory autoimmune conditions.
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