Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• Regulatory T cells (Tregs) are crucial for immune system balance and preventing autoimmune diseases.
• The transcription factor Foxp3 is essential for Treg development and function.
• Understanding Foxp3 expression dynamics is key to controlling immune responses.

Purpose of the Study:

• To create a novel mouse model for visualizing and studying Foxp3 expression in vivo.
• To identify previously unknown Foxp3-expressing cell populations.
• To investigate the induction of Foxp3 expression and Treg function.

Main Methods:

• Generation of a bicistronic reporter mouse model with a red fluorescent protein knocked into the endogenous Foxp3 locus.
• Analysis of Foxp3 expression in various lymphocyte populations using the reporter system.
• In vitro induction of Foxp3 expression and suppressive function in CD4 T cells using TGF-beta.
• Adoptive transfer experiments to assess the conversion of non-Foxp3-expressing CD4 T cells.

Main Results:

• The reporter mouse model successfully visualized Foxp3 expression across different immune cell types.
• Previously unidentified Foxp3-expressing cells were discovered.
• Transforming growth factor-beta (TGF-beta) was shown to induce de novo Foxp3 expression and suppressive function in activated CD4 T cells.
• Non-Foxp3-expressing CD4 T cells did not convert to Foxp3-expressing cells after adoptive transfer.

Conclusions:

• The developed Foxp3 bicistronic reporter knockin mouse model is a valuable tool for studying Treg biology.
• This model facilitates the identification and characterization of novel Treg populations.
• The findings provide insights into the regulation of Foxp3 expression and Treg function by TGF-beta.