Identification of 14-dehydroergosterol as a novel anti-inflammatory compound inducing tolerogenic dendritic cells. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Ano, Yasuhisa; Ikado, Kumiko; Shindo, Kazutoshi; Koizumi, Hideki; Fujiwara, Daisuke
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 11
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-14446-1
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Tolerogenic dendritic cells (DCs) have the ability to induce regulatory T cells and play an important role in preventing chronic inflammatory and autoimmune diseases. We have identified a novel compound, 14-dehydroergosterol, from Koji, a Japanese traditional food material fermented with fungi. 14-dehydroergosterol is an ergosterol analogue with a conjugated double bond, but the activity of 14-dehydroergosterol is much higher than that of ergosterol. 14-dehydroergosterol induces the conversion of murine bone marrow (BM)-derived DCs and differentiated DCs into tolerogenic DCs, in which the production of IL-12 is suppressed and that of IL-10 is increased. In a co-culture experiment, DCs treated with 14-dehydroergosterol induced the conversion of naïve CD4-positive T cells into regulatory T cells. In a murine model of multiple sclerosis, experimental autoimmune encephalopathy, 14-dehydroergosterol suppressed the clinical score and inflammatory responses of myeloid DCs and T cells to myelin oligodendrocyte glycoprotein. 14-dehydroergosterol-treated human DCs induced from PBMCs also showed a tolerogenic phenotype. This is the first report to identify a novel compound, 14-dehydroergosterol, that induces DCs to convert to a tolerogenic type. 14-dehydroergosterol is contained in various fermented foods based on Koji, so 14-dehydroergosterol might be a helpful aid to prevent chronic inflammatory and autoimmune diseases.