Variation in the CTLA4 3′UTR has phenotypic consequences for autoreactive T cells and associates with genetic risk for type 1 diabetes

Genes and Immunity

Volumn 17, Issue 1, 2016, Pages 75-78

  De Jong, V M ^a   Zaldumbide, A ^a   Van Der Slik, A R ^a   Laban, S ^a   Koeleman, B P C ^b   Roep, B O ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DACTINOMYCIN; DINUCLEOTIDE; GLUCOSE 6 PHOSPHATASE; INTERLEUKIN 15; INTERLEUKIN 2; MESSENGER RNA; 3' UNTRANSLATED REGION; CTLA4 PROTEIN, HUMAN;

3' UNTRANSLATED REGION; ARTICLE; AUTOIMMUNITY; CLINICAL ASSESSMENT; COMPARATIVE STUDY; CONTROLLED STUDY; DINUCLEOTIDE REPEAT; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; EVIDENCE BASED PRACTICE; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOME ANALYSIS; HIGH RISK PATIENT; HUMAN; IMMUNOREGULATION; INSULIN DEPENDENT DIABETES MELLITUS; MAJOR CLINICAL STUDY; PHENOTYPIC VARIATION; POSTTRANSCRIPTIONAL GENE SILENCING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN STRUCTURE; REGULATORY MECHANISM; RISK ASSESSMENT; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE; GENETIC PREDISPOSITION; GENETICS; IMMUNOLOGY; RNA PROCESSING;

3' UNTRANSLATED REGIONS; CTLA-4 ANTIGEN; DIABETES MELLITUS, TYPE 1; DINUCLEOTIDE REPEATS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; RNA PROCESSING, POST-TRANSCRIPTIONAL; T-LYMPHOCYTES;

EID: 84955332058     PISSN: 14664879     EISSN: 14765470     Source Type: Journal    
DOI: 10.1038/gene.2015.51     Document Type: Article

References (30)

1. Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 1992; 356: 607-609.
2. Koulova L, Clark EA, Shu G, Dupont B. The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells. J Exp Med 1991; 173: 759-762.
3. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995; 182: 459-465.
4. Ise W, Kohyama M, Nutsch KM, Lee HM, Suri A, Unanue ER et al. CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms. Nat Immunol 2010; 11: 129-135.
5. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008; 322: 271-275.
6. Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 2011; 332: 600-603.
7. Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet 2011; 378: 412-419.
8. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009; 41: 703-707.
9. Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 2008; 359: 2767-2777.
10. Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 2010; 42: 508-514.
11. Rueda B, Zhernakova A, Lopez-Nevot MA, Gomez-Garcia M, Ortega E, Pinero A et al. CTLA4/CT60 polymorphism is not relevant in susceptibility to autoimmune inflammatory intestinal disorders. Hum Immunol 2005; 66: 321-325.
12. Chen Z, Brant SR, Li C, Shrestha UK, Jiang T, Zhou F et al. CTLA4 -1661A/G and 3'UTR long repeat polymorphisms are associated with ulcerative colitis and influence CTLA4 mRNA and protein expression. Genes Immun 2010; 11: 573-583.
13. Zhernakova A, Eerligh P, Barrera P, Wesoly JZ, Huizinga TW, Roep BO et al. CTLA4 is differentially associated with autoimmune diseases in the Dutch population. Hum Genet 2005; 118: 58-66.
14. Ligers A, Teleshova N, Masterman T, Huang WX, Hillert J. CTLA-4 gene expression is influenced by promoter and exon 1 polymorphisms. Genes Immun. 2001; 2: 145-152.
15. Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423: 506-511.
16. Hao S, Baltimore D. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat Immunol 2009; 10: 281-288.
17. Anderson P. Post-transcriptional control of cytokine production. Nat Immunol 2008; 9: 353-359.
18. de Jong VM, Zaldumbide A, van der Slik AR, Persengiev SP, Roep BO, Koeleman BP. Post-transcriptional control of candidate risk genes for type 1 diabetes by rare genetic variants. Genes Immun 2013; 14: 58-61.
19. Morahan G, Huang D, Ymer SI, Cancilla MR, Stephen K, Dabadghao P et al. Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet 2001; 27: 218-221.
20. Roep BO, Kallan AA, Hazenbos WL, Bruining GJ, Bailyes EM, Arden SD et al. T-cell reactivity to 38 kD insulin-secretory-granule protein in patients with recentonset type 1 diabetes. Lancet 1991; 337: 1439-1441.
21. Lindstein T, June CH, Ledbetter JA, Stella G, Thompson CB. Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science 1989; 244: 339-343.
22. Gough SC, Walker LS, Sansom DM. CTLA4 gene polymorphism and autoimmunity. Immunol Rev 2005; 204: 102-115.
23. Mayans S, Lackovic K, Nyholm C, Lindgren P, Ruikka K, Eliasson M et al. CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden. BMC Med Genet 2007; 8: 3.
24. Purohit S, Podolsky R, Collins C, Zheng W, Schatz D, Muir A et al. Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes. J Autoimmune Dis 2005; 2: 8.
25. Atabani SF, Thio CL, Divanovic S, Trompette A, Belkaid Y, Thomas DL et al. Association of CTLA4 polymorphism with regulatory T cell frequency. Eur J Immunol 2005; 35: 2157-2162.
26. Esposito L, Hunter KMD, Clark J, Rainbow DB, Stevens H, Denesha J et al. Investigation of Soluble and Transmembrane CTLA-4 Isoforms in Serum and Microvesicles. J Immunol 2014; 193: 889-900.
27. Vijayakrishnan L, Slavik JM, Illes Z, Greenwald RJ, Rainbow D, Greve B et al. An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity 2004; 20: 563-575.
28. 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.
29. Gu M, Kakoulidou M, Giscombe R, Pirskanen R, Lefvert AK, Klareskog L et al. Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis. Clin Immunol 2008; 128: 374-381.
30. Dudbridge F. Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered 2008; 66: 87-98.