New high-throughput screen identifies targeted regulators of immune suppressor cells

Qian Wei, researcher in MATRIX, and her colleagues recently published a new article in the ACS Chemical Biology Journal. The article, High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells, presents an automated, high-throughput method for identifying small molecules that selectively regulate regulatory T cells (Tregs), a critical cell type that controls immune system balance. The screening method may contribute to the development of more precise immunotherapies for cancer and autoimmune diseases.

Tregs play a dual role in health and disease. While they prevent harmful autoimmunereactions, excessive Treg activity can suppress immune responses against tumours. The function and identity of Tregs are governed by the transcription factor FoxP3, a molecule that has long been considered difficult to target with drugs.

In the new study, Qian Wei et al established a flow‑cytometry‑based phenotypic screening platform that directly measures FoxP3 levels in human primary T cells. By integrating automated cell handling, robust data analysis, and built‑in filters for compounds with toxicity and autofluorescence, the system enables reliable screening of large drug collections in biologically relevant cells.

Using a library of more than 1,500 FDA‑ and EMA‑approved drugs, the team identified multiple compounds that alter FoxP3 expression and Treg function. One key finding was the identification of ethoxyquin, a small antioxidant molecule, as a potent down‑regulator of FoxP3. Functional experiments showed that ethoxyquin-treated Tregs lost their ability to suppress effector T cells, restoring immune activity.

Wei et al further expanded on this result by testing chemical analogues of ethoxyquin. Several derivatives showed stronger effects on FoxP3 expression and Treg suppression, while maintaining low toxicity, revealing clear relationships between structure and activity that can guide future drug development.

Beyond the individual compounds identified, the study’s main contribution is the screening platform itself. It offers a scalable and versatile tool for discovering FoxP3 regulators and supports the broader goal of fine‑tuning immune responses rather than eliminating immune cell populations outright.

The paper follows up previous work from the group and represents an important step toward safer, more targeted immunomodulatory therapies.

Read thefull article:

Wei Q, Hajjar E, Cornillot-Clément S, Solli E, García-Díaz N, Landskron J, Gade A, Ahmad R, Taskén K. High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells. ACS Chem Biol. 2026 Apr 3. doi: 10.1021/acschembio.5c01019. Epub ahead of print.

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