Sulforaphane protects from T cell-mediated autoimmune disease by inhibition of IL-23 and IL-12 in dendritic cells.
J Immunol, 2014/4/15;192(8):3530-9.
Geisel J[1], Brück J, Glocova I, Dengler K, Sinnberg T, Rothfuss O, Walter M, Schulze-Osthoff K, Röcken M, Ghoreschi K
Affiliations
PMID: 24639357DOI: 10.4049/jimmunol.1300556
Impact factor: 5.426
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.
MeSH terms
Animals; Autoimmune Diseases; Cell Differentiation; Cluster Analysis; Cytokines; DNA; Dendritic Cells; Encephalomyelitis, Autoimmune, Experimental; Female; Gene Expression Profiling; Gene Expression Regulation; Heme Oxygenase-1; Interleukin-12; Interleukin-23; Isothiocyanates; Lymphocyte Activation; Mice; NF-kappa B; Phenotype; Protein Binding; Sulfoxides; T-Lymphocyte Subsets; Th1 Cells; Th17 Cells
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