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

被引：27

作者：

Brueck, Juergen ^{[1
]}

Holstein, Julia ^{[1
]}

Glocova, Ivana ^{[1
]}

Seidel, Ursula ^{[1
]}

Geisel, Julia ^{[1
]}

Kanno, Toshio ^{[2
]}

Kumagai, Jin ^{[2
]}

Mato, Naoko ^{[2
]}

Sudowe, Stephan ^{[3
]}

Widmaier, Katja ^{[1
]}

Sinnberg, Tobias ^{[1
]}

Yazdi, Amir S. ^{[1
]}

Eberle, Franziska C. ^{[1
]}

Hirahara, Kiyoshi ^{[2
]}

Nakayama, Toshinori ^{[2
]}

Roecken, Martin ^{[1
]}

Ghoreschi, Kamran ^{[1
]}

机构：

[1] Eberhard Karls Univ Tubingen, Univ Med Ctr, Dept Dermatol, D-72076 Tubingen, Germany

[2] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan

[3] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Dermatol, D-55101 Mainz, Germany

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

NF-KAPPA-B; DENDRITIC CELLS; GENE-EXPRESSION; AIRWAY INFLAMMATION; DIETARY CURCUMIN; MURINE MODEL; C-REL; IL-12; STAT3; ENCEPHALOMYELITIS;

D O I：

10.1038/srep44482

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

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