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Updated: Dec 15, 2025
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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
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The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.
Jing Yang1, Ping Wei2, Joseph Barbi3
1Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
EMBO Reports
|July 10, 2020
Summary
The ubiquitin-specific peptidase 44 (USP44) deubiquitinates and stabilizes the transcription factor forkhead box P3 (FOXP3), crucial for regulatory T cell (Treg) function. USP44 is vital for Treg efficacy in inflammatory diseases and cancer.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Forkhead box P3 (FOXP3) is essential for regulatory T cell (Treg) development and immune homeostasis.
- FOXP3 regulation by ubiquitination/deubiquitination is known in natural Tregs (nTregs), but unclear in induced Tregs (iTregs).
Purpose of the Study:
- To identify novel deubiquitinases targeting FOXP3 in induced Tregs (iTregs).
- To elucidate the role of USP44 in FOXP3 regulation and Treg function.
Main Methods:
- Yeast three-hybrid screening to identify FOXP3-interacting proteins.
- Co-immunoprecipitation and Western blotting to confirm USP44-FOXP3 interaction and ubiquitination status.
- In vitro and in vivo assays using USP44-deficient Tregs in models of inflammatory disease and cancer.
Main Results:
- USP44 was identified as a novel deubiquitinase for FOXP3, specifically removing K48-linked ubiquitin chains.
- Transforming growth factor-beta (TGF-β) induces USP44 expression during iTreg differentiation.
- USP44 cooperates with USP7 to stabilize and deubiquitinate FOXP3, enhancing Treg function.
- Tregs lacking USP44 exhibit reduced efficacy in vitro and in vivo models of inflammation and cancer.
Conclusions:
- USP44 is a key regulator of FOXP3 stability and Treg function.
- USP44 plays a critical role in immune homeostasis and in controlling inflammatory diseases and cancer.
- USP44 represents a potential therapeutic target for enhancing anti-cancer immunotherapy by modulating Treg function.
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