Homeobox protein Hhex negatively regulates Treg cells by inhibiting Foxp3 expression and function
Sung Woong Jang1, Soo Seok Hwang1,2, Hyeong Su Kim1
1Department of Life Science, Sogang University, 04107 Seoul, Korea.
Summary
Homeobox protein Hhex suppresses regulatory T (Treg) cells. Overexpressing Hhex inhibits Treg cell function and differentiation, offering potential therapeutic strategies for immune-related diseases.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Regulatory T (Treg) cells are crucial for immune homeostasis.
- Treg cell-mediated immunosuppression hinders treatments for cancer and infections.
Purpose of the Study:
- To identify novel regulators of Treg cell function.
- To investigate the role of homeobox protein Hhex in Treg cell biology.
Main Methods:
- Investigated Hhex expression in Treg versus conventional T (Tconv) cells.
- Utilized retroviral overexpression of Hhex in Treg cells.
- Assessed Treg cell differentiation, stability, and immunosuppressive function in vitro and in vivo.
- Analyzed Hhex binding to gene promoters using molecular techniques.
Main Results:
- Hhex expression is lower in Treg cells compared to Tconv cells, repressed by TGF-β/Smad3 signaling.
- Hhex overexpression inhibits induced and thymic Treg cell differentiation and stability by reducing Foxp3 expression.
- Hhex-overexpressing Treg cells exhibit impaired immunosuppressive activity and fail to prevent experimental colitis.
- Hhex directly represses the transcription of Foxp3 and other Treg signature genes (Il2ra, Ctla4).
Conclusions:
- Hhex acts as a negative regulator of Treg cell differentiation and function.
- Hhex inhibits Treg cell activity primarily through the repression of Foxp3.
- Hhex represents a potential therapeutic target for modulating Treg cell responses in disease.
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