A Phenotypic Screening Approach Using Human Treg Cells Identified Regulators of Forkhead Box p3 Expression

ACS Chemical Biology
Mei DingRajneesh Malhotra

Abstract

Regulatory T (Treg) cells, expressing the transcription factor forkhead box p3 (FOXP3), are the key cells regulating peripheral autoreactive T lymphocytes by suppressing effector T cells. FOXP3+ Treg cells play essential roles controlling immune responses in autoimmune diseases and cancer. Several clinical approaches (e.g., polyclonal expansion of Treg cells with anti-CD3 and anti-CD28 coated beads in the presence of drugs) are under evaluation. However, expression of FOXP3, recognized as the master regulator of Treg cells, in induced Treg cells have been shown to be instable, and molecular targets involved in regulating FOXP3 expression and Treg cell function have not been well-defined. Thus, new targets directly regulating FOXP3 expression and the expression of its downstream genes (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA4)) have the potential to stabilize the Treg cell phenotype and function. This report describes the development of an automated medium-throughput 384-well plate flow cytometry phenotypic assay meauring the protein expression of FOXP3 and CTLA4 in human Treg cells. Screening a library of 4213 structurally diverse compounds allowed us to identify a variety of compounds regulating FOXP3 and CTLA4...Continue Reading

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Citations

May 20, 2020·SLAS Discovery·Mei DingLovisa Holmberg Schiavone
Aug 28, 2020·Frontiers in Oncology·Anastasios Dimou, Konstantinos N Syrigos
Oct 16, 2020·Expert Opinion on Drug Discovery·Mei Ding, David Baker
Jul 6, 2021·Frontiers in Genetics·Jana StichtStefan Konigorski
Sep 6, 2020·Cell Chemical Biology·Fabien VincentMarie-Claire Peakman

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