Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells

Hammer A, Waschbisch A, Knippertz I, Zinser E, Berg J, Joerg S, Kuhbandner K, David C, Pi J, Bayas A, Lee DH, Haghikia A, Gold R, Steinkasserer A, Linker R (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 8

Pages Range: 1922

DOI: 10.3389/fimmu.2017.01922

Abstract

To date, the intracellular signaling pathways involved in dendritic cell (DC) function are poorly understood. The antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been shown to affect maturation, function, and subsequent DC-mediated T cell responses of murine and human DCs. In experimental autoimmune encephalomyelitis (EAE), as prototype animal model for a T helper cell-mediated autoimmune disease, antigen presentation, cytokine production, and costimulation by DCs play a major role. We explore the role of Nrf2 in DC function, and DC-mediated T cell responses during T cell-mediated autoimmunity of the central nervous system using genetic ablation and pharmacological activation in mice and men to corroborate our data in a translational setting. In murine and human DCs, monomethyl fumarate induced Nrf2 signaling inhibits DC maturation and DC-mediated T cell proliferation by reducing inflammatory cytokine production and expression of costimulatory molecules. In contrast, Nrf2-deficient DCs generate more activated T helper cells (Th1/Th17) but fewer regulatory T cells and foster T cell proliferation. Transfer of DCs with Nrf2 activation during active EAE reduces disease severity and T cell infiltration. Our data demonstrate that Nrf2 signaling modulates autoimmunity in murine and human systems via inhibiting DC maturation and function thus shedding further light on the mechanism of action of antioxidative stress pathways in antigen-presenting cells.

Authors with CRIS profile

Involved external institutions

Klinikum Augsburg Germany (DE) China Medical University (CMU) / 中國醫藥大學 Taiwan (TW) Ruhr-Universität Bochum (RUB) Germany (DE)

How to cite

APA:

Hammer, A., Waschbisch, A., Knippertz, I., Zinser, E., Berg, J., Joerg, S.,... Linker, R. (2017). Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells. Frontiers in Immunology, 8, 1922. https://doi.org/10.3389/fimmu.2017.01922

MLA:

Hammer, Anna, et al. "Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells." Frontiers in Immunology 8 (2017): 1922.

BibTeX: Download