title: Genetic polymorphism in FOXP3 gene: imbalance in regulatory T-cell role and development of human diseases.
abstract: The FOXP3 gene encodes a transcription factor thought to be important for the development and function of regulatory T cells (Treg cells). These cells are involved in the regulation of T cell activation and therefore are essential for normal immune homeostasis. Signals from microenvironment have a profound influence on the maintenance or progression of diseases. Thus, Tregs have an important marker protein, FOXP3, though it does not necessarily confer a Treg phenotype when expressed. FOXP3 polymorphisms that occur with high frequency in the general populations have been studied in common multifactorial human diseases. Dysfunction of FOXP3 gene product could result in lack of Treg cells and subsequently chronically activated CD4+ T cells which express increased levels of several activation markers and cytokines, resulting in some autoimmune diseases. In contrast, high Treg levels have been reported in peripheral blood, lymph nodes, and tumour specimens from patients with different types of cancer. The present study discusses the polymorphisms located in intron, exon and promoter regions of FOXP3 which have already been investigated by many researchers. FOXP3 has received considerable attention in attempts to understand the molecular aspect of Treg cells. Therefore, in the present study, the relationship between genetic polymorphism of FOXP3 in Treg-cell role and in disease development are reviewed considering the interactive effect of genetic factors.
authors: Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Campus Universitário CEP 86051-990 Londrina, Brazil.
authors: Julie Massayo Maeda
authors: JM
authors: Oda
authors: Bruna Karina Banin
authors: BK
authors: Hirata
authors: Roberta Losi
authors: RL
authors: Guembarovski
authors: Maria Angelica Ehara
authors: MA
authors: Watanabe
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D004715:Endometriosis / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
references: Nat Immunol. 2011 Jan;12(1):14-6
references: 21170000
references: Immunogenetics. 2011 Jul;63(7):409-15
references: 21472440
references: J Exp Med. 2011 Jul 4;208(7):1485-99
references: 21670203
references: Hum Immunol. 2005 Aug;66(8):869-73
references: 16216670
references: Immunol Rev. 2006 Aug;212:99-113
references: 16903909
references: Sci Signal. 2011 Feb 01;4(158):pe4
references: 21285410
references: Nat Rev Immunol. 2008 Jul;8(7):523-32
references: 18566595
references: Cell. 2006 Jul 28;126(2):375-87
references: 16873067
references: Nat Immunol. 2009 Nov;10(11):1170-7
references: 19767756
references: Hum Mol Genet. 2003 Sep 15;12(18):2249-54
references: 12915441
references: Clin Exp Immunol. 2010 Dec;162(3):402-6
references: 20942809
references: Immunity. 2011 Apr 22;34(4):479-91
references: 21458306
references: Nature. 2007 Feb 22;445(7130):936-40
references: 17237761
references: Mol Cell Biol. 2004 Jan;24(2):809-22
references: 14701752
references: Nature. 2009 Mar 19;458(7236):351-6
references: 19182775
references: J Exp Med. 2007 Jul 9;204(7):1543-51
references: 17591856
references: Nat Genet. 2001 Jan;27(1):20-1
references: 11137993
references: J Immunol. 2003 Dec 15;171(12):6323-7
references: 14662827
references: Cancer Genet Cytogenet. 2009 Apr 1;190(1):40-2
references: 19264232
references: Science. 2009 Nov 13;326(5955):986-91
references: 19797626
references: Clin Dev Immunol. 2007;2007:89017
references: 18317533
references: Nat Rev Immunol. 2009 Feb;9(2):83-9
references: 19114986
references: Nat Immunol. 2005 Apr;6(4):345-52
references: 15785760
references: Lupus. 2011 Feb;20(2):137-43
references: 21078762
references: Immunity. 2009 Oct 16;31(4):609-20
references: 19800266
references: Structure. 2006 Jan;14(1):159-66
references: 16407075
references: Cell Cycle. 2007 Jun 15;6(12):1432-6
references: 17592252
references: Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9631-6
references: 16769892
references: Nat Immunol. 2008 Feb;9(2):194-202
references: 18157133
references: Nat Genet. 2001 Jan;27(1):68-73
references: 11138001
references: PLoS Biol. 2007 Feb;5(2):e38
references: 17298177
references: Clin Chim Acta. 2007 Sep;384(1-2):171-3
references: 17612516
references: J Mol Endocrinol. 2006 Aug;37(1):97-104
references: 16901927
references: Cell. 2008 May 30;133(5):775-87
references: 18510923
references: Adv Drug Deliv Rev. 2006 Oct 1;58(8):948-61
references: 17070961
references: Fertil Steril. 2011 Jun;95(7):2223-7
references: 21481380
references: Nature. 2007 Feb 22;445(7130):931-5
references: 17237765
references: J Med Genet. 2002 Aug;39(8):537-45
references: 12161590
references: Nat Immunol. 2007 Mar;8(3):277-84
references: 17220892
references: Nat Rev Immunol. 2011 Jun 24;11(7):438
references: 21701515
references: Nature. 2007 Apr 5;446(7136):685-9
references: 17377532
references: Int Immunol. 2007 Jul;19(7):825-35
references: 17586580
references: Hum Immunol. 2009 Nov;70(11):930-4
references: 19679154
references: Ann N Y Acad Sci. 2005 Jun;1051:218-28
references: 16126962
references: Rheumatology (Oxford). 2007 Aug;46(8):1263-5
references: 17526924
references: J Immunol. 2008 Apr 1;180(7):4785-92
references: 18354202
references: Breast Cancer Res Treat. 2011 Nov;130(2):645-55
references: 21717105
references: J Clin Invest. 2006 Jun;116(6):1713-22
references: 16741580
references: J Clin Oncol. 2009 Apr 10;27(11):1735-6
references: 19255314
references: Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):515-21
references: 17989528
references: Curr Opin Rheumatol. 2003 Jul;15(4):430-5
references: 12819471
references: J Biol Chem. 2003 Jul 4;278(27):24259-68
references: 12692134
references: PLoS One. 2009 Nov 18;4(11):e7890
references: 19924293
references: J Immunol. 2006 Sep 1;177(5):3133-42
references: 16920951
references: Genes Immun. 2011 Oct;12(7):559-67
references: 21654845
references: Nat Rev Immunol. 2004 Nov;4(11):889-99
references: 15516968
references: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5138-43
references: 15790681
references: Immunogenetics. 2003 Jun;55(3):149-156
references: 12750858
references: Nature. 2008 May 8;453(7192):236-40
references: 18368049
references: Haemophilia. 2010 May;16(3):469-73
references: 20015215
references: J Dermatol Sci. 2010 Jan;57(1):51-6
references: 19880293
references: Eur J Immunol. 2007 Sep;37(9):2378-89
references: 17694575
references: Cancer Metastasis Rev. 2010 Dec;29(4):569-79
references: 20830504
references: Hum Immunol. 2011 Oct;72(10):926-9
references: 21763379
references: Genes Immun. 2009 Dec;10 Suppl 1:S74-84
references: 19956106
references: Immunity. 2005 Mar;22(3):329-41
references: 15780990
references: Clin Dev Immunol. 2012;2012:896458
references: 21876709
references: J Autoimmun. 2007 Jun;28(4):201-7
references: 17418529
references: Cancer Sci. 2011 Nov;102(11):1972-6
references: 21812857
references: Nat Rev Immunol. 2007 Apr;7(4):305-10
references: 17380159
references: J Immunol. 2006 Mar 15;176(6):3593-602
references: 16517728
references: Diabetes. 2004 Jul;53(7):1911-4
references: 15220219
references: Allergy. 2010 Jul;65(7):865-74
references: 20028375
references: J Cell Mol Med. 2010 Jan;14(1-2):226-41
references: 20414968
references: J Autoimmun. 2006 Sep;27(2):140-4
references: 16996248
references: Int Immunol. 2008 Aug;20(8):1041-55
references: 18567616
references: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4571-6
references: 17360565