Details

Autor(en) / Beteiligte

• Namdari, Haideh
• Izad, Maryam
• Rezaei, Farhad
• Amirghofran, Zahra

Titel

Thymol as a reciprocal regulator of T cell differentiation: Promotion of regulatory T cells and suppression of Th1/Th17 cells

Ist Teil von

• International immunopharmacology, 2019-02, Vol.67, p.417-426

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Regulatory T cells (Tregs) are critical for maintaining immune response and enhancing their differentiation has therapeutic implications for autoimmune diseases. In this study, we investigated the effects of thymol a well-known monoterpene from Thyme on differentiation and function of Tregs. In vitro generation of Tregs from purified naïve CD4+CD25− T cells in the presence of thymol was carried out. Suppressor activity of generated Tregs was examined by changes in the proliferation of CFSE-labeled conventional T cells. Thymol promotes differentiation of naïve CD4+CD25− T cells to CD4+CD25+Foxp3+ Tregs [66.9–71.8% vs. control (47%)] and increased intensity of Foxp3 expression on Tregs (p < 0.01). In functional assay, an increased immune suppression by thymol-induced Tregs (≈2.5 times of untreated Tregs) was detected. For in vivo study, thymol was intraperitoneally administered to ovalbumin (Ova)-immunized mice. Flow cytometry assessment of spleens from thymol-treated Ova-immunized mice showed increased number of CD4+ Foxp3+ Tregs (>8%, p < 0.01(and decreased levels of CD4+T-bet+ Th1 and CD4+RORγt+ Th17 cells resulted in significant decreased Th1/Treg and Th17/Treg ratios. In ex vivo Ova challenge of splenocytes from thymol-treated Ova-immunized mice, similarly higher levels of CD4+ Foxp3+ Tregs, and also elevated TGF-β expression in CD4+Foxp3+ population (48.1% vs. 18.9% in untreated Ova-immunized group) and reduced IFN-γ-producing CD4+T-bet+ T cells and IL-17-producing CD4+RORγt+ T cells were detected. This led to marked decreased ratios of IFNγ/TGF-β and IL-17/TGF-β expressions. In conclusion, this study revealed thymol as a compound with enhancing effects on Treg differentiation and function, which may have potential benefits in treatment of immune-mediated diseases with Th1/Th17 over-activation. •Thymol could improve Tregs differentiation and function in vitro.•Thymol up-regulated Tregs and down-regulated Th1 and Th17 cells in Ova-immunized mice.•Thymol enhanced TGF-β expression in Tregs and decreased IFNγ and IL-17 levels in Th1 and Th17 cells in vivo.•Thymol could change the Th1/Tregs and Th17/Tregs balance toward Treg differentiation.