کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2512739 1118375 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Systematic evaluation of 640 FDA drugs for their effect on CD4+Foxp3+ regulatory T cells using a novel cell-based high throughput screening assay
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Systematic evaluation of 640 FDA drugs for their effect on CD4+Foxp3+ regulatory T cells using a novel cell-based high throughput screening assay
چکیده انگلیسی

Regulatory T cells (Treg), which play a pivotal role in maintaining immune homeostasis by suppressing the proliferation of effector T cells, have great therapeutic potential for autoimmune diseases and transplantation. However, progress on their clinical application has been hampered by the lack of high throughput screening (HTS) strategies for the systematic and rapid evaluation of existing drugs and the identification of novel drug candidates. In this report, we present an innovative in vitro HTS assay using CD4+ T cells from Foxp3-GFP transgenic mice that specifically express the GFP signal in Foxp3+ Treg cells detectable by FACS analysis in a high throughput manner. Systematic evaluation of 640 FDA-approved drugs revealed that 70 drugs increased the number of Treg cells with suppression function only in the presence of TGFβ, 75 drugs increased Treg numbers even in the absence of TGFβ, and 32 drugs increased Treg numbers synergistically with TGFβ. The identified Treg-promoting drugs include those previously known to induce Treg (rapamycin and retinoic acid), statins, glucocorticoids and drugs in many other categories. Furthermore, Treg cells cultured with the identified drugs possess surface and intracellular markers characteristic of natural Treg cells and possess suppressive function. These results suggest that this Treg HTS assay can be used to screen compound libraries to identify novel chemical entities for Treg-based immune therapies.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 85, Issue 10, 15 May 2013, Pages 1513–1524
نویسندگان
, , , , , , ,