title: Nutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation.
abstract: The 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.
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brück
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Holstein
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Glocova
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidel
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Geisel
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kanno
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Kumagai
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Mato
authors.affiliation: Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, 55101 Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Sudowe
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Widmaier
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Sinnberg
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Amir S
authors.initials: AS
authors.lastname: Yazdi
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Franziska C
authors.initials: FC
authors.lastname: Eberle
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
authors.affiliation: Department of Dermatology, University Medical Center of the Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghoreschi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental; D051547:Heme Oxygenase-1 / Q000235:genetics*; D007111:Immunity, Cellular / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053759:Interleukin-23 / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D010047:Ovalbumin / Q000633:toxicity; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics*; D058504:Th17 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D053759:Interleukin-23; D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D010047:Ovalbumin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D003474:Curcumin