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Foxp3 interacts with c-Rel to mediate NF-κB repression

Louiza Loizou1, Kristian G Andersen, Alexander G Betz

  • 1MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.

Plos One
|April 15, 2011
PubMed

Insights

The transcription factor Foxp3 interacts with c-Rel, a key NF-κB component, influencing regulatory T cell function. Specific Foxp3 regions mediate binding to c-Rel and NFAT, impacting T cell development and suppression.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Foxp3 is a critical transcription factor for regulatory T cell (Treg) development and function.
  • Foxp3 interacts with various transcriptional regulators and epigenetic modifiers to orchestrate the Treg transcriptional program.
  • The precise molecular mechanisms of Foxp3 interactions, particularly with NF-κB family members, require further elucidation.

Purpose of the Study:

  • To investigate the direct interaction between Foxp3 and the NF-κB component c-Rel.
  • To identify the specific domains of Foxp3 involved in binding to c-Rel and NFAT.
  • To understand the functional implications of the Foxp3-c-Rel interaction in Treg biology.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Deletion mutagenesis of Foxp3 to map interaction domains.
  • Analysis of Foxp3 and c-Rel binding affinities.

Main Results:

  • Foxp3 directly engages with the NF-κB component c-Rel, either alone or in a complex.
  • The N-terminal region of Foxp3 is essential for c-Rel binding, but not NFAT binding.
  • Deletion of the Foxp3 forkhead domain abolishes NFAT interaction but preserves c-Rel binding.

Conclusions:

  • Foxp3 forms a specific complex with c-Rel, mediated by its N-terminal region.
  • Distinct domains of Foxp3 govern interactions with c-Rel and NFAT, suggesting differential regulatory roles.
  • These findings provide insights into the dynamic regulation of Foxp3 activity by c-Rel during Treg development and homeostasis.

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