Tetrastigma hemsleyanum alleviates sarcoidosis through metabolomic regulation and Th17/Treg immune homeostasis

This review focuses on the biology of T helper 17 (Th17) and regulatory T (Treg) cells and their role in inflammatory diseases, such as rheumatoid arthritis. Th17 cells represent a pro-inflammatory subset whereas Treg cells have an antagonist effect. Their developmental pathways are reciprocally interconnected and there is an important plasticity between Th17 and Treg cells. These features implicate that the Th17/Treg balance plays a major role in the development and the disease outcomes of animal model and human autoimmune/inflammatory diseases. During these diseases, this balance is disturbed and this promotes the maintenance of inflammation. Targeting the Th17/Treg imbalance can be performed at different levels such as inhibition of pro-inflammatory cytokines and their receptors, of pathogenic cells or their specific signaling pathways. Conversely, direct effects include administration or induction of protective cells, or stimulation of their specific pathways. Several clinical trials are underway and some positive results have been obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

Oxidative stress and low antioxidant levels are implicated in the aetiology of sarcoidosis, an inflammatory disease. Quercetin is a potent dietary antioxidant that also displays anti-inflammatory activities. Consequently, the aim is to examine the effect of quercetin supplementation on markers of oxidative stress and inflammation in sarcoidosis. A double-blind intervention study has been conducted with two groups of non-smoking, un-treated sarcoidosis patients, matched for age and gender. One group was given 4x500 mg quercetin (n = 12) orally within 24 h, the other one placebo (n = 6). Plasma malondialdehyde levels were used as marker of oxidative damage, plasma ratios of TNFα/IL-10 and IL-8/IL-10 as pro-inflammatory markers. Quercetin supplementation improved the antioxidant defence, indicated by the increased total plasma antioxidant capacity. Moreover, quercetin supplementation also reduced markers of oxidative stress and inflammation in the blood of sarcoidosis patients. The effects of quercetin supplementation appeared to be more pronounced when the levels of the oxidative stress and inflammation markers were higher at baseline. Sarcoidosis patients might benefit from the use of antioxidants, such as quercetin, to reduce the occurring oxidative stress as well as inflammation. The effects of long-term use of antioxidant supplementation in sarcoidosis, using e.g. quercetin, on improvement of lung function remain to be investigated. (www.clinicaltrials.gov; NCT-00402623). Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The T helper 17 (Th17) cells contain a dynamic subset of CD4+ T-cells that are able to develop into other different lineage subsets, including the Th1-like Th17 cells. These cells co-express retinoic acid-related orphan receptor gamma t (RORγt) and transcription factor T-box-expressed-in-T-cells (T-bet) and produce both interleukin (IL)-17 and interferon (IFN)-γ. Recent reports have shown that Th1-like Th17 cells play crucial roles in the pathogenesis of autoimmune diseases such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, as well as, some primary immunodeficiency with autoimmune features. Here, the actual mechanisms for Th17 cells plasticity to Th1-like Th17 cells are discussed and reviewed in association to the role that Th1-like Th17 cells have on inflammatory and autoimmune disorders.