Small organic molecules accelerate the expansion of regulatory T cells
| Autor: | Xiaoming Zhang, Shafiullah Khan, Muhammad Waqar Hameed, Saifullah Afridi, Abdul Wajid Khalil, Musarrat Adnan, Jamshed Iqbal, M. A. Shahid, Daniel C. Hoessli, Zhiyuan Wu, Zafar Iqbal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
chemistry [Phenols]
pharmacology [Small Molecule Libraries] 01 natural sciences Biochemistry T-Lymphocytes Regulatory chemistry.chemical_compound Mice pharmacology [Alkaloids] chemistry [Alkaloids] Drug Discovery Receptor Cytotoxicity Mice Inbred BALB C Molecular Structure Chemistry Small molecules FOXP3 hemic and immune systems Regulatory T cells Small molecule Cell biology Molecular Docking Simulation ddc:540 T(reg) cells proliferators chemistry [Small Molecule Libraries] FOXP3(+) chemical and pharmacologic phenomena Small Molecule Libraries Structure-Activity Relationship Alkaloids Phenols Animals Humans Propidium iodide drug effects [T-Lymphocytes Regulatory] Molecular Biology PI3K/AKT/mTOR pathway Cell Proliferation T(reg) cells receptors drug effects [Cell Proliferation] Dose-Response Relationship Drug pharmacology [Phenols] 010405 organic chemistry Organic Chemistry T-cell receptor In vitro 0104 chemical sciences Mice Inbred C57BL 010404 medicinal & biomolecular chemistry NIH 3T3 Cells |
| Zdroj: | Bioorganic chemistry 111, 104908-(2021). doi:10.1016/j.bioorg.2021.104908 |
| DOI: | 10.1016/j.bioorg.2021.104908 |
| Popis: | The regulatory T cells (Treg cells) expressing CD4 + CD25 + FOXP3 + markers are indispensable for the initiation of immune homeostasis and tolerance to self-antigens in both mice and humans. A decrease in regulatory T cells leads to various autoimmune pathologies. Herein, we report three low molecular weight, small organic molecules as a new series of Treg proliferators TRP-1-3. These small molecules were tested for their proliferative effect on regulatory T cells. It was found that TRP-1 (Oleracein E) strongly accelerates the Treg proliferation in vitro in a concentration-dependent manner. The effect was evident for all subsets of Treg cells tested, including naturally occurring, thymus-derived and peripherally-induced or adaptive Treg, indicating an effect independent of the maturation site. Importantly, increased Treg cells numbers by TRP-1 correlated with improved CD4 + CD25 + FOXP3 + expression in vitro, while propidium iodide-based staining showed low TRP-1-induced cytotoxicity. Molecular docking plus simulation studies of these TRP-1-3 with IL-2R, mTOR and TCR receptors suggest a TCR-based Treg cells activation mechanism. Because of its high Treg cells activities and low cellular cytotoxicity, TRP-1-3 may be useful in stimulating ex-vivo/in-vivo, Treg cell-specific responses for therapeutic applications. |
| Databáze: | OpenAIRE |
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