FoxP3: a life beyond regulatory T cells

Area of Science:

• Immunology
• Cell Biology
• Genetics

Background:

• The established view posits Forkhead box P3 (FoxP3) exclusively functions within regulatory T cells (Treg).
• FoxP3-expressing Treg are considered essential for immune homeostasis and survival in mice.
• The dogma suggests FoxP3's sole role is in Treg function.

Purpose of the Study:

• To challenge the exclusive role of FoxP3 in regulatory T cells.
• To investigate the broader expression and function of FoxP3 beyond Treg.
• To elucidate the multifaceted causes of autoimmune disease in FoxP3-mutant mice.

Main Methods:

• Review of existing literature and experimental data on FoxP3 expression and function.
• Analysis of thymopoiesis in mice with FoxP3 mutations in different cell types.
• Correlation of FoxP3 mutation effects with Treg deficiency and homeostatic proliferation.

Main Results:

• Evidence indicates FoxP3 expression extends beyond regulatory T cells.
• FoxP3 mutations in thymic stromal cells lead to impaired thymopoiesis.
• Impaired thymopoiesis results in increased homeostatic proliferation of T cells.

Conclusions:

• The lethal autoimmune phenotype in germline FoxP3-mutant mice results from a combination of Treg deficiency and enhanced homeostatic proliferation.
• FoxP3's role in immune regulation is more complex than previously understood, involving non-Treg compartments.
• This review re-evaluates the critical functions of FoxP3 in immune system development and homeostasis.