Dataset Information

Negligible Effect of Sodium Chloride on the Development and Function of TGF-?-Induced CD4+ Foxp3+ Regulatory T Cells.

ABSTRACT: High-salt diets inhibit the suppressive function of thymus-derived natural regulatory T cells (tTreg). Transforming growth factor ? (TGF-?)-induced ex vivo regulatory T cells (iTreg) comprise another Treg subset that exhibits similarities and differences with tTreg. Here, we demonstrate that iTregs are completely stable and fully functional under high salt conditions. High salt does not influence the development, differentiation, and functional activities of iTreg but affects Foxp3 stability and function of tTreg in vitro and in vivo. In addition, high salt does not significantly change the transcription profiles of the iTreg signature or pro-inflammatory genes. Therefore, we conclude that iTreg, unlike tTreg, are stable and functional in the presence of high salt. Our findings provide additional evidence that iTreg may have different biological features from tTreg and suggest a greater potential for clinical utility in patients with autoimmune diseases, in which the complicated role of environmental factors, including diet, must be considered.

SUBMITTER: Luo Y

PROVIDER: S-EPMC6948355 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Negligible Effect of Sodium Chloride on the Development and Function of TGF-β-Induced CD4<sup>+</sup> Foxp3<sup>+</sup> Regulatory T Cells.

Luo Yang Y Xue Youqiu Y Wang Julie J Dang Junlong J Fang Qiannan Q Huang Gonghua G Olsen Nancy N Zheng Song Guo SG

Cell reports 20190201 7

High-salt diets inhibit the suppressive function of thymus-derived natural regulatory T cells (tTreg). Transforming growth factor β (TGF-β)-induced ex vivo regulatory T cells (iTreg) comprise another Treg subset that exhibits similarities and differences with tTreg. Here, we demonstrate that iTregs are completely stable and fully functional under high salt conditions. High salt does not influence the development, differentiation, and functional activities of iTreg but affects Foxp3 stability and ...[more]

PMID: 30759396

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Project description:Psoriasis is an autoimmune and inflammatory skin disease affecting around 2-3% of the world's population. Patients with psoriasis need extensive treatments with global immunosuppressive agents that may cause severe side effects. Esculetin, a type of coumarins, is an active ingredient extracted mainly from the bark of Fraxinus rhynchophylla, which has been used to treat inflammatory and autoimmune diseases in China. However, the antipsoriatic effects of esculetin have not been reported. In this study, we aimed to investigate the effects of esculetin on psoriatic skin inflammation in a mouse model and explored the potential molecular mechanisms underlying its action. We found that esculetin ameliorated the skin lesion and reduced PASI scores as well as weight loss in imiquimod-induced psoriasis-like mice, accompanied with weakened proliferation and differentiation of keratinocytes and T cell infiltration in esculetin-treated psoriatic mice. In addition, esculetin reduced the frequency of CD8+CD44highCD62Llow effector T cells in psoriatic mice. In contrast, it increased the frequency of CD4+Foxp3+ Tregs in both lymph nodes and spleens of the psoriatic mice while promoting the differentiation of CD4+CD25- T cells into CD4+Foxp3+ Tregs in vitro. Interestingly, depleting CD4+Foxp3+ Tregs largely reversed esculetin-mediated reduction in PASI scores, indicating that esculetin attenuates murine psoriasis mainly by inducing CD4+Foxp3+ Tregs. Furthermore, the mRNA levels of proinflammatory cytokines in the psoriatic mouse skin, including IL-6, IL-17A, IL-22, IL-23, TNF-?, and IFN-?, were dramatically decreased by the treatment with esculetin. Finally, we found that esculetin inhibited the phosphorylation of IKK? and P65 in the psoriatic skin, suggesting that it inhibits the activation of NF-?B signaling. Thus, we have demonstrated that esculetin attenuates psoriasis-like skin lesion in mice and may be a potential therapeutic candidate for the treatment of psoriasis in clinic.

Dataset Information

Negligible Effect of Sodium Chloride on the Development and Function of TGF-?-Induced CD4+ Foxp3+ Regulatory T Cells.

Publications

Negligible Effect of Sodium Chloride on the Development and Function of TGF-β-Induced CD4<sup>+</sup> Foxp3<sup>+</sup> Regulatory T Cells.

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