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

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-γ 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-α. 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.

• Authors: Julia Geisel, Jürgen Brück, Ivana Glocova, Katja Dengler, Tobias Sinnberg, Oliver Rothfuss, Michael Walter, Klaus Schulze-Osthoff, Martin Röcken, Kamran Ghoreschi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 192 Issue 8 Pg. 3530-9 (Apr 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 24639357 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-23
• Isothiocyanates
• NF-kappa B
• Sulfoxides
• Interleukin-12
• DNA
• Heme Oxygenase-1
• sulforaphane

Topics

• Animals
• Autoimmune Diseases (immunology, metabolism, prevention & control)
• Cell Differentiation (drug effects)
• Cluster Analysis
• Cytokines (biosynthesis)
• DNA (metabolism)
• Dendritic Cells (drug effects, immunology, metabolism)
• Encephalomyelitis, Autoimmune, Experimental (immunology, metabolism, prevention & control)
• Female
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (metabolism)
• Interleukin-12 (genetics, metabolism)
• Interleukin-23 (genetics, metabolism)
• Isothiocyanates (administration & dosage, pharmacology)
• Lymphocyte Activation (drug effects, immunology)
• Mice
• NF-kappa B (metabolism)
• Phenotype
• Protein Binding (drug effects)
• Sulfoxides
• T-Lymphocyte Subsets (drug effects, immunology, metabolism)
• Th1 Cells (cytology, drug effects, immunology, metabolism)
• Th17 Cells (cytology, drug effects, immunology, metabolism)