Forkhead Box Protein 3: Difference between revisions
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[[Image:Picturefoxp3.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> 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:Picturefoxp3.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> 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> %%%%% | ||
| **FOXP3** upregulates a number of genes like Cd25 and Ctla4 and represses other genes like IL-2 and Ptpn22.<ref>PMID: 17237761</ref> Further, 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> | ||
Talk about alignment with [[FOXP2]] and fix the morph. | Talk about alignment with [[FOXP2]] and fix the morph. | ||
Revision as of 23:09, 27 April 2012
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] 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.[2] 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.[3] 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.[4] %%%%% **FOXP3** upregulates a number of genes like Cd25 and Ctla4 and represses other genes like IL-2 and Ptpn22.[5] Further, 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.[6] Talk about alignment with FOXP2 and fix the morph.
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ReferencesReferences
- ↑ Josefowicz SZ, Rudensky A. Control of regulatory T cell lineage commitment and maintenance. Immunity. 2009 May;30(5):616-25. PMID:19464984 doi:10.1016/j.immuni.2009.04.009
- ↑ Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001 Jan;27(1):20-1. PMID:11137993 doi:10.1038/83713
- ↑ Williams LM, Rudensky AY. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol. 2007 Mar;8(3):277-84. Epub 2007 Jan 14. PMID:17220892 doi:10.1038/ni1437
- ↑ Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003 Apr;4(4):330-6. Epub 2003 Mar 3. PMID:12612578 doi:10.1038/ni904
- ↑ Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature. 2007 Feb 22;445(7130):936-40. Epub 2007 Jan 21. PMID:17237761 doi:10.1038/nature05563
- ↑ Rudra D, Egawa T, Chong MM, Treuting P, Littman DR, Rudensky AY. Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells. Nat Immunol. 2009 Nov;10(11):1170-7. Epub 2009 Sep 20. PMID:19767756 doi:10.1038/ni.1795