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Thymol As a Reciprocal Regulator of T Cell Differentiation: Promotion of Regulatory T Cells and Suppression of Th1/Th17 Cells Publisher Pubmed



Namdari H1 ; Izad M2 ; Rezaei F3 ; Amirghofran Z1, 4
Authors
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Authors Affiliations
  1. 1. Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
  2. 2. Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Autoimmune Diseases Research Center, Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Source: International Immunopharmacology Published:2019


Abstract

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 naive 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 naive 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. © 2018 Elsevier B.V.