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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
Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function.
Xiaomin Song1, Bin Li, Yan Xiao
1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China 200031.
Cell Reports
|July 21, 2012
Summary
The FOXP3 coiled-coil domain structure reveals transient dimerization crucial for regulatory T cell function. Key residues and acetylation regulate this dimerization, explaining IPEX syndrome mutations.
Area of Science:
- Immunology
- Structural Biology
- Molecular Biology
Background:
- FOXP3 is a critical transcription factor for regulatory T cell (Treg) function.
- Dysregulation of FOXP3 is associated with immune disorders like IPEX syndrome.
Purpose of the Study:
- To elucidate the structural basis of FOXP3 function through its coiled-coil domain.
- To understand how mutations and posttranslational modifications affect FOXP3 activity and Treg function.
Main Methods:
- X-ray crystallography to determine the FOXP3 coiled-coil domain structure.
- Structure-guided mutagenesis to investigate protein-protein interactions and functional significance.
- In vitro and in vivo assays to assess Treg function.
Main Results:
- The crystal structure reveals a loose or transient dimeric association of the FOXP3 coiled-coil domain.
- FOXP3 homodimerization via the coiled-coil domain is essential for Treg function.
- Identified key residues (K250, K252) and reversible lysine acetylation as regulators of FOXP3 dimer stability and conformation.
- Provided structural and mechanistic explanations for IPEX syndrome-associated mutations.
Conclusions:
- FOXP3 homodimerization is a critical regulatory mechanism for Treg function.
- Posttranslational modifications, such as acetylation, dynamically control FOXP3 activity.
- Structural insights into FOXP3 oligomerization and regulation offer a mechanistic basis for immune dysregulation in IPEX syndrome.
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