Hi
I'm looking for supplements that down regulate th-17. I have Hashimoto's Thyroiditis and recently read this abstract:
http://onlinelibrary...2425.x/abstract
T helper 17(Th17) cell is a new subset of CD4+ T cells that produce a proinflammatory cytokine interleukin-17 (IL-17). Th17 cells have recently been shown to play a critical role in many autoimmune diseases that had previously been thought to be Th1 dominant. Although Hashimoto’s thyroiditis (HT) was thought to be a Th1-type disease, the contributions of Th17 cells to the pathogenesis remain unclear. In this study, we investigated the expression levels of Th1/Th17 cell-associated factors in peripheral blood mononuclear cells (PBMC) and plasma from patients with HT by quantitative real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Our results showed that the expression levels of Th1 cells-related T-bet and interferon-γ (IFN-γ) mRNA in PBMC from HT significantly decreased. However, the mRNA of Th17 coherent retinoic acid-related orphan nuclear receptor gamma t (RORγt) and IL-17 in patients with HT increased. In addition, a negative correlation between T-bet and RORγt mRNA expression was found in patients with HT, and the similar phenomena also appeared on the levels of mRNA and plasma concentration between IFN-γ and IL-17. It suggested that Th17 cells rather than Th1 cells predominated among patients suffering from HT, and Th17 cells might be involved in the pathogenesis of HT.
So far I think the following might be helpful but I'm not sure and Im note sure if there's anything better.
Vitamin D3
http://www.jbc.org/c.../38751.abstract
Vitamin D Suppresses Th17 Cytokine Production by Inducing C/EBP Homologous Protein (CHOP) Expression*
Abstract
Vitamin D has been shown to have immunomodulatory function, but the molecular basis for it has not been well understood. In this study, we found that vitamin D receptor expression was induced in a CD4+ effector T cell lineage, Th17 cells, which required the transcription factors, RORα, RORγt, and STAT3. Treatment of mice with an active ligand of vitamin D receptor (VDR), 1,25-dihydroxyvitamin D3 (1,25D3), ameliorated experimental autoimmune encephalomyelitis, accompanied with reduced IL-17 and IL-17F expression. In vitro, treatment of CD4+ T cells with the physiological doses of 1,25D3 preferentially inhibited cytokine production by Th17 cells, in a VDR-dependent manner, without affecting the expression of transcription factors or surface molecules. Moreover, at these concentrations, cytokine expression was suppressed only at protein but not at mRNA levels. Stimulation of Th17 cells with 1,25D3, in a concentration-dependent manner, induced the expression of C/EBP homologous protein (CHOP), a molecule involved in endoplasmic reticulum stress and translational inhibition. In addition, overexpression of CHOP in developing Th17 cells suppressed their cytokine production. Our results suggest a novel, post-transcriptional mechanism whereby Th17 cytokines are inhibited by VDR, which may underscore future therapeutic usage of vitamin D in treatment of autoimmune diseases.
Berberine
http://www.jimmunol....3/1855.abstract
Regulation of Th1 and Th17 Cell Differentiation and Amelioration of Experimental Autoimmune Encephalomyelitis by Natural Product Compound Berberine
Abstract
Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4+Foxp3+ regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-κB activity in CD11b+ APCs. BBR treatment completely abolished the encephalitogenicity of MOG35–55-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG35–55-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.
Zinc
http://intimm.oxford...t/22/5/375.full
Zinc suppresses Th17 development via inhibition of STAT3 activation
Abstract
Zinc (Zn) is an essential trace metal required by many enzymes and transcription factors for their activity or the maintenance of their structure. Zn has a variety of effects in the immune responses and inflammation, although it has not been well known how Zn affects these reactions on the molecular basis. We here showed that Zn suppresses Th17-mediated autoimmune diseases at lest in part by inhibiting the development of Th17 cells via attenuating STAT3 activation. In mice injected with type II collagen to induce arthritis, Zn treatment inhibited Th17 cell development. IL-6-mediated activation of STAT3 and in vitro Th17 cell development were all suppressed by Zn. Importantly, Zn binding changed the α-helical secondary structure of STAT3, disrupting the association of STAT3 with JAK2 kinase and with a phospho-peptide that included a STAT3-binding motif from the IL-6 signal transducer gp130. Thus, we conclude that Zn suppresses STAT3 activation, which is a critical step for Th17 development.
Curcumin
http://www.ncbi.nlm....pubmed/19539560
Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production
Abstract
Experimental autoimmune encephalomylitis (EAE), an animal mode of multiple sclerosis (MS), was previously considered that be mediated by Th1 cells. However, a number of recent studies provided strong evidence that T helper cells that produce IL-17 play a dominant role in the pathogenesis of EAE. Curcumin (1,7-Bis 94-hydroxy-3-methoxyphenyl)-1,6 heptadiene-3, 5-di-one) is a naturally occurring polyphenolic phytochemical isolated from the rhizome of the medicinal plant Curcuma longa. It has been strongly implicated as an anti-inflammatory agent, but the precise mechanisms of its action are largely unknown. In the present study, we have investigated the efficacy and mechanism of curcumin against EAE. The treatment of Lewis rats with curcumin significantly reduced the clinical severity of EAE, and had a dramatic reduction in the number of inflammatory cells infiltration in the spinal cord. The proliferation of the MBP-reaction lymphocyte also was reduced in a curcumin dose-dependent manner. Furthermore, the mRNA expression of the cytokine profiles was assessed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), revealing the dramatic decrease of IL-17, TGF-β, IL-6, IL-21, STAT3, and RORγt expression in curcumin-treated groups and STAT3-phosphorylation also was inhibited. These findings indicated that curcumin amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-21, RORγt signaling and inhibition STAT3-phosphorylation, suggests it is useful in the treatment of MS and other Th17 cell-mediated inflammatory diseases.
If anybody knows of any other supplements to add or comments on the ones I listed I'd appreciate it. Also if I'm barking up the wrong tree with this th-17 stuff please let me know. Understanding this stuff is not my strength.
Thanks
