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BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology
Achia Khatun1,2, Xiaopeng Wu1,2, Fu Qi3
1Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 17, 2023
Summary
The transcription factor BATF is crucial for regulatory T (Treg) cell function and stability. Loss of BATF in Tregs leads to autoimmune disease, highlighting its therapeutic potential.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmunity
Background:
- Regulatory T (Treg) cells are essential for preventing autoimmune responses.
- Treg function depends on the transcription factor FOXP3 and exists in resting (rTreg) and activated (aTreg) subsets.
- TCR signaling drives aTreg differentiation and homeostasis, but Treg transcriptional regulation remains unclear.
Purpose of the Study:
- To investigate the role of the transcription factor BATF in Treg differentiation, homeostasis, and stability.
- To elucidate the molecular mechanisms by which BATF regulates Treg function.
- To assess the therapeutic potential of targeting BATF in autoimmune diseases.
Main Methods:
- Investigated BATF's role in Treg differentiation and function in mice lacking BATF in Tregs.
- Analyzed Treg-specific gene regulation by BATF.
- Examined the epigenetic regulation of the Foxp3 locus by BATF, focusing on CNS2 demethylation and accessibility.
Main Results:
- Mice lacking BATF in Tregs developed multiorgan autoimmune pathology.
- BATF is required for Treg differentiation, homeostasis, and FOXP3 expression stabilization across tissues.
- BATF directly regulates Treg-specific genes and epigenetically controls Foxp3 locus accessibility, crucial for Treg stability.
Conclusions:
- BATF is a critical transcriptional regulator essential for Treg differentiation, homeostasis, and maintaining FOXP3 expression stability.
- BATF's epigenetic regulation of the Foxp3 locus is vital for Treg function.
- BATF represents a promising therapeutic target for autoimmune diseases due to its role in Treg stability.
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