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RESEARCH PRODUCT

Nutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation

Martin RöckenUrsula SeidelJulia GeiselJulia HolsteinJürgen BrückAmir S. YazdiKiyoshi HiraharaTobias SinnbergToshio KannoKatja WidmaierIvana GlocovaToshinori NakayamaFranziska C. EberleNaoko MatoStephan SudoweJin KumagaiKamran Ghoreschi

subject

0301 basic medicineSTAT3 Transcription FactorCurcuminEncephalomyelitis Autoimmune ExperimentalOvalbuminEncephalomyelitisInterleukin-23ArticleAutoimmune Diseases03 medical and health sciencesMiceImmune systemTh2 CellsmedicineInterleukin 23Gene silencingAnimalsPhosphorylationSTAT3Autoimmune diseaseInflammationImmunity CellularMultidisciplinarybiologyChemistryMembrane ProteinsDendritic Cellsmedicine.diseaseCell biologyHeme oxygenase030104 developmental biologybiology.proteinPhosphorylationTh17 CellsHeme Oxygenase-1

description

AbstractThe nutritional curcumin (CUR) is beneficial in cell-mediated autoimmune diseases. The molecular mechanisms underlying this food-mediated silencing of inflammatory immune responses are poorly understood. By investigating antigen-specific immune responses we found that dietary CUR impairs the differentiation of Th1/Th17 cells in vivo during encephalomyelitis and instead promoted Th2 cells. In contrast, feeding CUR had no inhibitory effect on ovalbumin-induced airway inflammation. Mechanistically, we found that CUR induces an anti-inflammatory phenotype in dendritic cells (DC) with enhanced STAT3 phosphorylation and suppressed expression of Il12b and Il23a. On the molecular level CUR readily induced NRF2-sensitive heme oxygenase 1 (HO-1) mRNA and protein in LPS-activated DC. HO-1 enhanced STAT3 phosphorylation, which enriched to Il12b and Il23a loci and negatively regulated their transcription. These findings demonstrate the underlying mechanism through which a nutritional can interfere with the immune response. CUR silences IL-23/Th17-mediated pathology by enhancing HO-1/STAT3 interaction in DC.

yearjournalcountryeditionlanguage
2017-03-14Scientific Reports
10.1038/srep44482http://dx.doi.org/10.1038/srep44482