Dehydrodiconiferyl alcohol (DHCA) modulates the differentiation of Th17 and Th1 cells and suppresses experimental autoimmune encephalomyelitis

•DHCA suppressed the differentiation of Th17 cells.•DHCA inhibited the RNA expression of IL-17/RORrt pathway.•DHCA ameliorated the severity of clinical symptoms in EAE. Dehydrodiconiferyl alcohol (DHCA), originally isolated from the stems of Cucurbita moschata, has previously been shown to exhibit a...

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Published in:	Molecular immunology Vol. 68; no. 2; pp. 434 - 444
Main Authors:	Lee, Junghun, Choi, Jinyong, Lee, Wonwoo, Ko, Kyeongryang, Kim, Sunyoung
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-12-2015
Subjects:	Animals Cell Differentiation - drug effects Cucurbita - metabolism Dehydrodiconiferyl alcohol (DHCA) Down-Regulation EAE Encephalomyelitis, Autoimmune, Experimental - drug therapy Encephalomyelitis, Autoimmune, Experimental - immunology IL-17 Interferon-gamma - biosynthesis Interleukin-17 - biosynthesis Male Mice Mice, Inbred C57BL Multiple Sclerosis - drug therapy Multiple Sclerosis - immunology NF-kappa B - antagonists & inhibitors NF-κB Nuclear Receptor Subfamily 1, Group F, Member 3 - biosynthesis Phenols - pharmacology Phenols - therapeutic use RORγt T-Box Domain Proteins - biosynthesis Th1 Th1 Cells - cytology Th1 Cells - drug effects Th1 Cells - immunology Th17 Th17 Cells - cytology Th17 Cells - drug effects Th17 Cells - immunology Transcription, Genetic - drug effects NF-κB IL-17 EAE Th1 Dehydrodiconiferyl alcohol (DHCA) Th17 RORγt
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Summary:	•DHCA suppressed the differentiation of Th17 cells.•DHCA inhibited the RNA expression of IL-17/RORrt pathway.•DHCA ameliorated the severity of clinical symptoms in EAE. Dehydrodiconiferyl alcohol (DHCA), originally isolated from the stems of Cucurbita moschata, has previously been shown to exhibit anti-adipogenic and anti-lipogenic effects in 3T3-L1 cells and primary mouse embryonic fibroblasts (MEFs) (Lee et al., 2012). Here, we investigated whether synthetic DHCA could suppress the CD4 T helper 17 (Th17)-mediated production of the interleukin (IL)-17 protein. The results from RT-qPCR suggest that DHCA-mediated down-regulation of IL-17 occurred at the transcriptional level by suppressing the expression of RAR-related orphan receptor (ROR)γt, the master transcription factor involved in the differentiation of Th17 cells. Furthermore, such inhibition was mediated by the suppression of NF-κB activity. DHCA also inhibited the Th1-mediated production of interferon (IFN) γ by controlling the expression of a key transcription factor known to regulate the production of this cytokine, T-bet. In the mouse experimental autoimmune encephalomyelitis (EAE) model, DHCA showed significant therapeutic effects by inhibiting the infiltration of immune cells into the spinal cords, decreasing the differentiation of pathogenic Th17 and Th1 cells, suppressing the expression of various pro-inflammatory cytokines, and eventually ameliorating the clinical symptoms of EAE mice. Taken together, our data indicate that DHCA may be a potential candidate as an agent for the control of Th17 and Th1-mediated inflammatory diseases.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0161-5890 1872-9142
DOI:	10.1016/j.molimm.2015.09.028