An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4+ T cells

Genes and Immunity

Volumn 12, Issue 2, 2011, Pages 116-125

  Long, S A ^a   Cerosaletti, K ^a   Wan, J Y ^b   Ho, J C ^a   Tatum, M ^a   Wei, S ^a   Shilling, H G ^a   Buckner, J H ^a  

^a BENAROYA RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

autoimmune disease; IL 2 receptor; PTPN2; single nucleotide polymorphism; STAT5

Indexed keywords

INTERLEUKIN 2 RECEPTOR; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 2; STAT5 PROTEIN;

ADULT; ALLELE; ARTICLE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; ENZYME ACTIVITY; FEMALE; GENETIC VARIABILITY; GENOTYPE; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE ACTIVATION;

ADULT; ALLELES; AUTOIMMUNITY; CD4-POSITIVE T-LYMPHOCYTES; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; INTERLEUKIN-2; MALE; PHENOTYPE; PHOSPHORYLATION; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 2; RECEPTORS, INTERLEUKIN-2; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR;

EID: 79952280031     PISSN: 14664879     EISSN: 14765470     Source Type: Journal    
DOI: 10.1038/gene.2010.54     Document Type: Article

References (47)

1. Sadlack B, Lohler J, Schorle H, Klebb G, Haber H, Sickel E et al. Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur J Immunol 1995; 25: 3053-3059.
2. Suzuki H, Kundig TM, Furlonger C, Wakeham A, Timms E, Matsuyama T et al. Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta. Science 1995; 268: 1472-1476.
3. Wellcome Trust Case Control Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature 2007; 44: 661-678.
4. Hakonarson H, Qu HQ, Bradfield JP, Marchand L, Kim CE, Glessner JT et al. A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study. Diabetes 2008; 57: 1143-1146.
5. Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 2007; 39: 857-864. (Pubitemid 47018195)
6. Dendrou CA, Wicker LS. The IL-2/CD25 Pathway Determines Susceptibility to T1D in Humans and NOD Mice. J Clin Immunol 2008; 6: 685-696.
7. Lowe CE, Cooper JD, Brusko T, Walker NM, Smyth DJ, Bailey R et al. Large-scale genetic fine mapping and genotypephenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet 2007; 9: 1074-1082. (Pubitemid 47340651)
8. Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL. Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. N Engl J Med 2007; 357: 851-862. (Pubitemid 47347319)
9. Maier LM, Lowe CE, Cooper J, Downes K, Anderson DE, Severson C et al. IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet 2009; 5: e1000322.
10. Matesanz F, Caro-Maldonado A, Fedetz M, Fernandez O, Milne RL, Guerrero M et al. IL2RA/CD25 polymorphisms contribute to multiple sclerosis susceptibility. J Neurol 2007; 254: 682-684. (Pubitemid 46781978)
11. Qu HQ, Verlaan DJ, Ge B, Lu Y, Lam KC, Grabs R et al. A cisacting regulatory variant in the IL2RA locus. J Immunol 2009; 183: 5158-5162.
12. Brand OJ, Lowe CE, Heward JM, Franklyn JA, Cooper JD, Todd JA et al. Association of the interleukin-2 receptor alpha (IL-2Ralpha)/CD25 gene region with Graves' disease using a multilocus test and tag SNPs. Clin Endocrinol (Oxf) 2007; 66: 508-512. (Pubitemid 46434929)
13. Harley JB, Alarcon-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008; 40: 204-210. (Pubitemid 351171405)
14. Long SA, Cerosaletti K, Bollyky PL, Tatum M, Shilling H, Zhang S et al. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4+CD25+ regulatory T cells of type 1 diabetic subjects. Diabetes 2010; 59: 407-415.
15. Malek TR. The biology of interleukin-2. Annu Rev Immunol 2008; 26: 453-479. (Pubitemid 351600382)
16. Kovanen PE, Leonard WJ. Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. Immunol Rev 2004; 202: 67-83. (Pubitemid 39576905)
17. Mustelin T, Vang T, Bottini N. Protein tyrosine phosphatases and the immune response. Nat Rev Immunol 2005; 5: 43-57. (Pubitemid 40070330)
18. Doody KM, Bourdeau A, Tremblay ML. T-cell protein tyrosine phosphatase is a key regulator in immune cell signaling: lessons from the knockout mouse model and implications in human disease. Immunol Rev 2009; 228: 325-341.
19. You T, Muise ES, Itie A, Michaliszyn E, Wagner J, Jothy S et al. Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice. J Exp Med 1997; 186: 683-693. (Pubitemid 27381533)
20. Galic S, Klingler-Hoffmann M, Fodero-Tavoletti MT, Puryer MA, Meng TC, Tonks NK et al. Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP. Mol Cell Biol 2003; 23: 2096-2108. (Pubitemid 36278819)
21. Simoncic PD, Lee-Loy A, Barber DL, Tremblay ML, McGlade CJ. The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr Biol 2002; 12: 446-453. (Pubitemid 34248890)
22. ten Hoeve J, de JI, Fu Y, Zhu W, Tremblay M, David M et al. Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol 2002: 22, 5662-5668. (Pubitemid 34815816)
23. van Vliet C, Bukczynska PE, Puryer MA, Sadek CM, Shields BJ, Tremblay ML et al. Selective regulation of tumor necrosis factor-induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase. Nat Immunol 2005; 6: 253-260. (Pubitemid 41724762)
24. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA et al. Genome-wide association study and metaanalysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009; 41: 703-707.
25. Arechiga AF, Habib T, He Y, Zhang X, Zhang ZY, Funk A et al. Cutting edge: The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol 2009; 182: 3343-3347.
26. Dendrou CA, Plagnol V, Fung E, Yang JH, Downes K, Cooper JD et al. Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource. Nat Genet 2009; 41: 1011-1015.
27. Rieck M, Arechiga A, Onengut-Gumuscu S, Greenbaum C, Concannon P, Buckner JH. Genetic Variation in PTPN22 Corresponds to Altered Function of T and B Lymphocytes. J Immunol 2007; 179: 4704-4710.
28. Passerini L, Allan SE, Battaglia M, Di Nunzio S, Alstad AN, Levings MK et al. STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells. Int Immunol 2008; 20: 421-431.
29. Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D et al. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 2006; 108: 1571-1579. (Pubitemid 44316124)
30. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 2001; 182: 18-32. (Pubitemid 33070205)
31. Araki M, Chung D, Liu S, Rainbow DB, Chamberlain G, Garner V et al. Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice. J Immunol 2009; 183: 5146-5157.
32. Vang T, Congia M, Macis MD, Musumeci L, Orru V, Zavattari P et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 2005; 37: 1317-1319. (Pubitemid 41722185)
33. Xu R, Yu Y, Zheng S, Zhao X, Dong Q, He Z et al. Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia. Blood 2005; 106: 3142-3149. (Pubitemid 41565912)
34. Veillette A, Rhee I, Souza CM, Davidson D. PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders. Immunol Rev 2009; 228: 312-324.
35. Korman BD, Kastner DL, Gregersen PK, Remmers EF. STAT4: genetics, mechanisms, and implications for autoimmunity. Curr Allergy Asthma Rep 2008; 8: 398-403.
36. Chistiakov DA, Voronova NV, Chistiakov PA. The crucial role of IL-2/IL-2RA-mediated immune regulation in the pathogenesis of type 1 diabetes, an evidence coming from genetic and animal model studies. Immunol Lett 2008; 118: 1-5.
37. Qu HQ, Montpetit A, Ge B, Hudson TJ, Polychronakos C. Toward further mapping of the association between the IL2RA locus and type 1 diabetes. Diabetes 2007; 56: 1174-1176. (Pubitemid 46525085)
38. Qu HQ, Bradfield JP, Belisle A, Grant SF, Hakonarson H, Polychronakos C. The type I diabetes association of the IL2RA locus. Genes Immun 2009; 10(Suppl 1): S42-S48.
39. Verlaan DJ, Ge B, Grundberg E, Hoberman R, Lam KC, Koka Vet al. Targeted screening of cis-regulatory variation in human haplotypes. Genome Res 2009; 19: 118-127.
40. Burchill MA, Yang J, Vogtenhuber C, Blazar BR, Farrar MA. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol 2007; 178: 280-290. (Pubitemid 46033611)
41. Tang Q, Adams JY, Penaranda C, Melli K, Piaggio E, Sgouroudis E et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 2008; 28: 687-697.
42. Moore F, Colli ML, Cnop M, Igoillo EM, Cardozo AK, Cunha DA et al. PTPN2, a candidate gene for type 1 diabetes, modulates interferon-gamma-induced pancreatic beta-cell apoptosis. Diabetes 2009; 58: 1283-1291.
43. Onengut-Gumuscu S, Ewens KG, Spielman RS, Concannon P. A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes Immun 2004; 5: 678-680. (Pubitemid 40045307)
44. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004; 36: 337-338. (Pubitemid 38437254)
45. Krutzik PO, Hale MB, Nolan GP. Characterization of the murine immunological signaling network with phosphospecific flow cytometry. J Immunol 2005; 175: 2366-2373. (Pubitemid 41113846)
46. Long SA, Buckner JH. Combination of rapamycin and IL-2 increases de novo induction of human CD4(+)CD25(+) FOXP3(+) T cells. J Autoimmun 2008; 30: 293-302.
47. R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing: Vienna, Austria, 2009 (http://www.R-project.org).