Nutritional Control of IL-23/Th17-mediated Autoimmune Disease Through HO-1/STAT3 Activation

Overview

Journal Sci Rep

Specialty Science

Date 2017 Mar 15

PMID 28290522

Citations 20

Authors

Jurgen Bruck

Julia Holstein

Ivana Glocova

Ursula Seidel

Julia Geisel

Toshio Kanno

Jin Kumagai

Naoko Mato

Stephan Sudowe

Katja Widmaier

Tobias Sinnberg

Amir S Yazdi

Franziska C Eberle

Kiyoshi Hirahara

Toshinori Nakayama

Martin Rocken

Kamran Ghoreschi

Affiliations

Soon will be listed here.

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.

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