Forkhead Box Protein 3 (
FOXP3) is a member of the
Forkhead transcription factor family. It is highly expressed in regulatory T (Treg) cells, a subset of CD4
+ T cells that play a critical role in suppressing immune responses, especially those mediated by autoreactive T cells.
[1] FOXP3 upregulates a number of genes like Cd25 and Ctla4 and represses other genes like IL-2 and Ptpn22.
[2] As with many transcription factors, it cooperates with a number of transcription factor partners to regulate gene expression, including NFAT1, which participates in the inducible expression of cytokine genes like IL-2, IL-4, and TNFα in T cells.
[3] A number of mutations to FOXP3 are known to result in a severe autoimmune disease known as IPEX (immune dysregulation, polyendocriopthy, enteropathy, X-linked). As FOXP3 is found on the X-chromosome, mutations to FOXP3 typically only display deleterious phenotypic traits in males, resulting in lymphocyte infiltration and wide spread inflammation in inphants.
[4] A similar pathology is also found in mice who carry nonsense mutations in the FOXP3 locus. These mutant mice are known as
scurfy mice. The targeted elimination of FOXP3
+ CD4
+ Tregs in adult mice has similar autoimmune dysfunction.
[5] Further, ectopic expression of FOXP3 in peripheral CD4
+CD25
- T cells equips these T cells with the ability to suppress the proliferation and effector functions of autoreactive T cells
in vivo.
[6]
The interaction of FOXP3 with NFAT1 and the FOXP3-NFAT1 target sequences found in IL-2 has been investigated extensively. The appears to form a with a and two unique oligonucleotides, each containing distinct FOXP sites.[7]
[7]
Talk about alignment with FOXP2 and fix the morph.
