NDLI: Sulforaphane protects from T cell-mediated autoimmune disease by inhibition of IL-23 and IL-12 in dendritic cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Schulze-Osthoff, Klaus Brück, Jürgen Dengler, Katja Ghoreschi, Kamran Rothfuss, Oliver Geisel, Julia Walter, Michael Glocova, Ivana Sinnberg, Tobias Röcken, Martin
Description	Author Affiliation: Geisel J ( Department of Dermatology, University Medical Center, Eberhard Karls University Tübingen, 72076 Tübingen, Germany)
Abstract	Sulforaphane (SFN), an isothiocyanate, is part of an important group of naturally occurring small molecules with anti-inflammatory properties. The published reports are best conceivable with an inhibition of T cell function, but the mode of action remains unknown. We therefore analyzed the effect of SFN on T cell-mediated autoimmune disease. Feeding mice with SFN protected from severe experimental autoimmune encephalomyelitis. Disease amelioration was associated with reduced IL-17 and IFN-Î³ expression in draining lymph nodes. In vitro, SFN treatment of T cells did not directly alter T cell cytokine secretion. In contrast, SFN treatment of dendritic cells (DCs) inhibited TLR4-induced IL-12 and IL-23 production, and severely suppressed Th1 and Th17 development of T cells primed by SFN-treated DCs. SFN regulated the activity of the TLR4-induced transcription factor NF-κB, without affecting the degradation of its inhibitor IκB- . Instead, SFN treatment of DCs resulted in strong expression of the stress response protein heme oxygenase-1 (HO-1), which interacts with and thereby inhibits NF-κB p65. Consistent with these findings, HO-1 bound to p65 and subsequently inhibited the p65 activity at the IL23a and IL12b promoters. Importantly, SFN suppressed Il23a and Il12b expression in vivo and silenced Th17/Th1 responses within the CNS. Thus, our data show that SFN improves Th17/Th1-mediated autoimmune disease by inducing HO-1 and inhibiting NF-κB p65-regulated IL-23 and IL-12 expression.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-04-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Autoimmune Diseases Immunology Metabolism Interleukin-12 Interleukin-23 Isothiocyanates Pharmacology T-lymphocyte Subsets Animals Prevention & Control Cell Differentiation Drug Effects Cluster Analysis Cytokines Biosynthesis Dendritic Cells Encephalomyelitis, Autoimmune, Experimental Gene Expression Profiling Gene Expression Regulation Heme Oxygenase-1 Genetics Administration & Dosage Lymphocyte Activation Mice Nf-kappa B Phenotype Protein Binding Th1 Cells Cytology Th17 Cells Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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