Open AccessNutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation
Author(s) -
Jürgen Brück,
Julia Holstein,
Ivana Glocova,
Ursula Jördis Eva Seidel,
Julia Geisel,
Toshio Kanno,
Jin Kumagai,
Naoko Mato,
Stephan Sudowe,
Katja Widmaier,
Tobias Sinnberg,
Amir S. Yazdi,
F. Éberlé,
Kiyoshi Hirahara,
Toshinori Nakayama,
Martin Röcken,
Kamran Ghoreschi
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep44482
Subject(s) - stat3 , immune system , interleukin 23 , ovalbumin , experimental autoimmune encephalomyelitis , phosphorylation , dendritic cell , biology , curcumin , inflammation , gene silencing , microbiology and biotechnology , immunology , interleukin 17 , chemistry , biochemistry , gene
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.