Forkhead Box Protein 3: Difference between revisions
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[[Image:Picturefoxp33.png|280px|left]] [[Forkhead Box Protein 3]] ('''FOXP3''') is a member of the [[Forkhead box protein|Forkhead transcription factor]] family. It is highly expressed in regulatory T (Treg) cells, a subset of CD4<sup>+</sup> T cells that play a critical role in suppressing immune responses, especially those mediated by autoreactive T cells.<ref>PMID:19464984</ref> FOXP3 upregulates a number of genes like Cd25 and Ctla4 and represses other genes like IL-2 and Ptpn22.<ref>PMID: 17237761</ref> 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.<ref>PMID: 19767756</ref> 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.<ref>PMID:11137993</ref> 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<sup>+</sup> CD4<sup>+</sup> Tregs in adult mice has similar autoimmune dysfunction.<ref>PMID:17220892</ref> Further, ectopic expression of FOXP3 in peripheral CD4<sup>+</sup>CD25<sup>-</sup> T cells equips these T cells with the ability to suppress the proliferation and effector functions of autoreactive T cells ''in vivo''.<ref>PMID:12612578</ref> | [[Image:Picturefoxp33.png|280px|left]] [[Forkhead Box Protein 3]] ('''FOXP3''') is a member of the [[Forkhead box protein|Forkhead transcription factor]] family. It is highly expressed in regulatory T (Treg) cells, a subset of CD4<sup>+</sup> T cells that play a critical role in suppressing immune responses, especially those mediated by autoreactive T cells.<ref>PMID:19464984</ref> FOXP3 upregulates a number of genes like Cd25 and Ctla4 and represses other genes like IL-2 and Ptpn22.<ref>PMID: 17237761</ref> 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.<ref>PMID: 19767756</ref> 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.<ref>PMID:11137993</ref> 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<sup>+</sup> CD4<sup>+</sup> Tregs in adult mice has similar autoimmune dysfunction.<ref>PMID:17220892</ref> Further, ectopic expression of FOXP3 in peripheral CD4<sup>+</sup>CD25<sup>-</sup> T cells equips these T cells with the ability to suppress the proliferation and effector functions of autoreactive T cells ''in vivo''.<ref>PMID:12612578</ref> | ||
The interaction of FOXP3 with NFAT1 and the FOXP3-NFAT1 target sequences found in IL-2 has been investigated extensively. The <scene name='Forkhead_Box_Protein_3/Foxp3_monomer/1'>Forkhead domain of FOXP3</scene> appears to form a domain swapped dimer with a dimerized rel homology region (RHR) of NFAT1 and two unique oligonucleotides, each containing distinct FOXP sites. | The interaction of FOXP3 with NFAT1 and the FOXP3-NFAT1 target sequences found in IL-2 has been investigated extensively. The <scene name='Forkhead_Box_Protein_3/Foxp3_monomer/1'>Forkhead domain of FOXP3</scene> appears to form a domain swapped dimer with a dimerized rel homology region (RHR) of NFAT1 and two unique oligonucleotides, each containing distinct FOXP sites.<ref name="Chen">PMID: 21458306</ref> | ||
Revision as of 21:22, 27 April 2012
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