High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells
Qian Wei1,2, Ehsan Hajjar1, Selma Cornillot-Clément1
1Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo 0424, Norway.
ACS Chemical Biology
|April 3, 2026
Summary
Researchers developed a new screening method to find small molecules that specifically target FoxP3, a key regulator in regulatory T cells (Tregs). This approach identifies potential therapies for autoimmune diseases and cancer by modulating Treg function without broad immune suppression.
Area of Science:
- Immunology
- Molecular Biology
- Drug Discovery
Background:
- Regulatory T cells (Tregs) are crucial for immune homeostasis, suppressing autoimmunity and antitumor responses.
- Targeting Tregs is a therapeutic strategy for autoimmune diseases and cancer.
- Need for specific Treg regulators to avoid off-target effects.
Purpose of the Study:
- Identify small molecules that specifically target the transcription factor FoxP3.
- Develop and validate a high-throughput screening assay for FoxP3 regulators.
Main Methods:
- High-throughput, flow-cytometry-based phenotypic screening of human primary T cells.
- Automated liquid handling pipeline measuring FoxP3 levels in CD4+ T cells.
- Data processing pipeline with algorithms for toxicity and autofluorescence filtering.
- Validation of hit candidates through functional analyses and characterization of chemical analogs.
Main Results:
- Developed a novel screening assay to identify FoxP3 regulators.
- Identified approved drugs and chemical analogs that modulate Treg function via FoxP3.
- Revealed structure-activity relationships for potent FoxP3 regulators.
Conclusions:
- The novel screening method successfully identifies FoxP3 regulators affecting Treg function.
- This approach offers a promising strategy for developing targeted therapies for immune-related diseases.
- Further characterization of identified compounds could lead to new therapeutic agents.
