Altered immune regulation in type 1 diabetes

Clinical and Developmental Immunology

Volumn 2013, Issue , 2013, Pages

  Zóka, András ^a   Muzes, Györgyi ^a   Somogyi, Anikó ^a   Varga, Tímea ^a   Szémán, Barbara ^a   Al Aissa, Zahra ^a   Hadarits, Orsolya ^b   Firneisz, Gábor ^a  

^a SEMMELWEIS UNIVERSITY OF MEDICINE   (Hungary)

^b SEMMELWEIS UNIVERSITY   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; INSULIN; LIRAGLUTIDE; VITAMIN D;

APOPTOSIS; AUTOIMMUNITY; DISEASE COURSE; ENVIRONMENTAL FACTOR; EPIGENETICS; HEREDITY; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; ANIMAL; ENVIRONMENT; GENETIC EPIGENESIS; GENETICS; IMMUNOLOGY; RISK FACTOR;

ANIMALS; APOPTOSIS; AUTOIMMUNITY; DIABETES MELLITUS, TYPE 1; ENVIRONMENT; EPIGENESIS, GENETIC; HUMANS; IMMUNE TOLERANCE; RISK FACTORS;

EID: 84884245268     PISSN: 17402522     EISSN: 17402530     Source Type: Journal    
DOI: 10.1155/2013/254874     Document Type: Review

References (149)

1. Taborsky G. J. Jr., Ahrén B., Havel P. J., Autonomic mediation of glucagon secretion during hypoglycemia: implications for impaired α -cell responses in type 1 diabetes. Diabetes 1998 47 7 995 1005 2-s2.0-2642593026 10.2337/diabetes.47.7.995
2. Blandino-Rosano M., Perez-Arana G., Mellado-Gil J. M., Segundo C., Aguilar-Diosdado M., Anti-proliferative effect of pro-inflammatory cytokines in cultured β cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide-1. Journal of Molecular Endocrinology 2008 41 1-2 35 44 2-s2.0-48949088649 10.1677/JME-07-0154
3. Hamilton-Williams E. E., Palmer S. E., Charlton B., Slattery R. M., Beta cell MHC class I is a late requirement for diabetes. Proceedings of the National Academy of Sciences of the United States of America 2003 100 11 6688 6693 2-s2.0-0037974762 10.1073/pnas.1131954100
4. Wang X., Zhang A., Liu Y., Chen S., Feng Z., Shang W., Maziarz M., Radtke J., Hampe C. S., Anti-idiotypic antibody specific to GAD65 autoantibody prevents type 1 diabetes in the NOD mouse. PLoS ONE 2012 7 2, article e32515 2-s2.0-84857573865 10.1371/journal.pone.0032515
5. Hauben E., Roncarolo M. G., Nevo U., Schwartz M., Beneficial autoimmunity in type 1 diabetes mellitus. Trends in Immunology 2005 26 5 248 253 2-s2.0-27644535371 10.1016/j.it.2005.03.004
6. Metcalfe K. A., Hitman G. A., Rowe R. E., Hawa M., Huang X., Stewart T., Leslie R. D. G., Concordance for type 1 diabetes in identical twins is affected by insulin genotype. Diabetes Care 2001 24 5 838 842 2-s2.0-0035345428
7. Redondo M. J., Jeffrey J., Fain P. R., Eisenbarth G. S., Orban T., Concordance for islet autoimmunity among monozygotic twins. The New England Journal of Medicine 2008 359 26 2849 2850 2-s2.0-58149096363 10.1056/NEJMc0805398
8. Orešič M., Simell S., Sysi-Aho M., Näntö-Salonen K., Seppänen-Laakso T., Parikka V., Katajamaa M., Hekkala A., Mattila I., Keskinen P., Yetukuri L., Reinikainen A., Lähde J., Suortti T., Hakalax J., Simell T., Hyöty H., Veijola R., Ilonen J., Lahesmaa R., Knip M., Simell O., Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes. The Journal of Experimental Medicine 2008 205 13 2975 2984 2-s2.0-59649105735 10.1084/jem.20081800
9. André I., Gonzalez A., Wang B., Katz J., Benoist C., Mathis D., Checkpoints in the progression of autoimmune disease: lessons from diabetes models. Proceedings of the National Academy of Sciences of the United States of America 1996 93 6 2260 2263 2-s2.0-0029978038 10.1073/pnas.93.6.2260
10. Todd J. A., Walker N. M., Cooper J. D., Smyth D. J., Downes K., Plagnol V., Bailey R., Nejentsev S., Field S. F., Payne F., Lowe C. E., Szeszko J. S., Hafler J. P., Zeitels L., Yang J. H. M., Vella A., Nutland S., Stevens H. E., Schuilenburg H., Coleman G., Maisuria M., Meadows W., Smink L. J., Healy B., Burren O. S., Lam A. A. C., Ovington N. R., Allen J., Adlem E., Leung H.-T., Wallace C., Howson J. M. M., Guja C., Ionescu-Tîrgovişte C., Simmonds M. J., Heward J. M., Gough S. C. L., Dunger D. B., Wicker L. S., Clayton D. G., Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nature Genetics 2007 39 7 857 864 2-s2.0-34347341846 10.1038/ng2068
11. Howson J. M. M., Walker N. M., Clayton D., Todd J. A., Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A. Diabetes, Obesity and Metabolism 2009 11 supplement 1 31 45 2-s2.0-58549090910 10.1111/j.1463-1326. 2008.01001.x
12. Huang J., Ellinghaus D., Franke A., Howie B., Li Y., 1000 genomes-based imputation identifies novel and refined associations for the wellcome trust case control consortium phase 1 data. European Journal of Human Genetics 2012 20 7 801 805 2-s2.0-84856351585 10.1038/ejhg.2012.3
13. Barrett J. C., Clayton D. G., Concannon P., Akolkar B., Cooper J. D., Erlich H. A., Julier C., Morahan G., Nerup J., Nierras C., Plagnol V., Pociot F., Schuilenburg H., Smyth D. J., Stevens H., Todd J. A., Walker N. M., Rich S. S., Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics 2009 41 6 703 707 2-s2.0-67349199566 10.1038/ng.381
14. Cooper J. D., Smyth D. J., Smiles A. M., Plagnol V., Walker N. M., Allen J. E., Downes K., Barrett J. C., Healy B. C., Mychaleckyj J. C., Warram J. H., Todd J. A., Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nature Genetics 2008 40 12 1399 1401 2-s2.0-56749183605 10.1038/ng.249
15. Burton P. R., Clayton D. G., Cardon L. R., Craddock N., Deloukas P., Duncanson A., Kwiatkowski D. P., McCarthy M. I., Ouwehand W. H., Samani N. J., Todd J. A., Donnelly P., Barrett J. C., Davison D., Easton D., Evans D., Leung H.-T., Marchini J. L., Morris A. P., Spencer C. C. A., Tobin M. D., Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007 447 7145 661 678 2-s2.0-34250025139 10.1038/nature05911
16. Hakonarson H., Grant S. F. A., Bradfield J. P., Marchand L., Kim C. E., Glessner J. T., Grabs R., Casalunovo T., Taback S. P., Frackelton E. C., Lawson M. L., Robinson L. J., Skraban R., Lu Y., Chiavacci R. M., Stanley C. A., Kirsch S. E., Rappaport E. F., Orange J. S., Monos D. S., Devoto M., Qu H.-Q., Polychronakos C., A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 2007 448 7153 591 594 2-s2.0-34547621758 10.1038/nature06010
17. Bradfield J. P., Qu H.-Q., Wang K., Zhang H., Sleiman P. M., Kim C. E., Mentch F. D., Qiu H., Glessner J. T., Thomas K. A., Frackelton E. C., Chiavacci R. M., Imielinski M., Monos D. S., Pandey R., Bakay M., Grant S. F. A., Polychronakos C., Hakonarson H., A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. PLoS Genetics 2011 7 9, article e1002293 2-s2.0-80053439315 10.1371/journal.pgen.1002293
18. Wallace C., Smyth D. J., Maisuria-Armer M., Walker N. M., Todd J. A., Clayton D. G., The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. Nature Genetics 2010 42 1 68 71 2-s2.0-73349115848 10.1038/ng.493
19. Grant S. F. A., Qu H.-Q., Bradfield J. P., Marchand L., Kim C. E., Glessner J. T., Grabs R., Taback S. P., Frackelton E. C., Eckert A. W., Annaiah K., Lawson M. L., George Otieno F., Santa E., Shaner J. L., Smith R. M., Skraban R., Imielinski M., Chiavacci R. M., Grundmeier R. W., Stanley C. A., Kirsch S. E., Waggott D., Paterson A. D., Monos D. S., Polychronakos C., Hakonarson H., Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes. Diabetes 2009 58 1 290 295 2-s2.0-63249115398 10.2337/db08-1022
20. Hakonarson H., Qu H.-Q., Bradfield J. P., Marchand L., Kim C. E., Glessner J. T., Grabs R., Casalunovo T., Taback S. P., Frackelton E. C., Eckert A. W., Annaiah K., Lawson M. L., Otieno F. G., Santa E., Shaner J. L., Smith R. M., Onyiah C. C., Skraban R., Chiavacci R. M., Robinson L. J., Stanley C. A., Kirsch S. E., Devoto M., Monos D. S., Grant S. F. A., Polychronakos C., A novel susceptibility locus for type 1 diabetes on chr12q13 identified by a genome-wide association study. Diabetes 2008 57 4 1143 1146 2-s2.0-42449094966 10.2337/db07-1305
21. Luning Prak E. T., Monestier M., Eisenberg R. A., B cell receptor editing in tolerance and autoimmunity. Annals of the New York Academy of Sciences 2011 1217 1 96 121 2-s2.0-79251571455 10.1111/j.1749-6632.2010.05877.x
22. McGargill M. A., Derbinski J. M., Hogquist K. A., Receptor editing in developing T cells. Nature Immunology 2000 1 4 336 341 2-s2.0-0034305741
23. Goodnow C. C., Sprent J., de St. Groth B. F., Vinuesa C. G., Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 2005 435 7042 590 597 2-s2.0-20444485767 10.1038/nature03724
24. Boettler T., von Herrath M., Protection against or triggering of type 1 diabetes? Different roles for viral infections. Expert Review of Clinical Immunology 2011 7 1 45 53 2-s2.0-78650552840 10.1586/eci.10.91
25. Vafiadis P., Bennett S. T., Todd J. A., Nadeau J., Grabs R., Goodyer C. G., Wickramasinghe S., Colle E., Polychronakos C., Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nature Genetics 1997 15 3 289 292 2-s2.0-0031018819 10.1038/ng0397-289
26. Fan Y., Rudert W. A., Grupillo M., He J., Sisino G., Trucco M., Thymus-specific deletion of insulin induces autoimmune diabetes. The EMBO Journal 2009 28 18 2812 2824 2-s2.0-70349194383 10.1038/emboj.2009.212
27. Klein L., Jovanovic K., Regulatory T cell differentiation: turning harmful into useful. Immunity 2012 37 3 441 443
28. Curotto de Lafaille M. A., Lafaille J. J., Natural and adaptive Foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 2009 30 5 626 635 2-s2.0-65549123867 10.1016/j.immuni.2009.05.002
29. Plagnol V., Howson J. M. M., Smyth D. J., Walker N., Hafler J. P., Wallace C., Stevens H., Jackson L., Simmonds M. J., Bingley P. J., Gough S. C., Todd J. A., Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genetics 2011 7 8, article e1002216 2-s2.0-80052311755 10.1371/journal.pgen.1002216
30. T1DBase-home page. June 2013, http://www.t1dbase.org/page/Welcome/display
31. Nolting J., Daniel C., Reuter S., Stuelten C., Li P., Sucov H., Kim B.-G., Letterio J. J., Kretschmer K., Kim H.-J., Von Boehmer H., Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. The Journal of Experimental Medicine 2009 206 10 2131 2139 2-s2.0-70350478405 10.1084/jem.20090639
32. Benson M. J., Pino-Lagos K., Rosemblatt M., Noelle R. J., All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. The Journal of Experimental Medicine 2007 204 8 1765 1774 2-s2.0-34547769253 10.1084/jem.20070719
33. Denning T. L., Wang Y.-C., Patel S. R., Williams I. R., Pulendran B., Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nature Immunology 2007 8 10 1086 1094 2-s2.0-34548764423 10.1038/ni1511
34. Josefowicz S. Z., Lu L.-F., Rudensky A. Y., Regulatory T cells: mechanisms of differentiation and function. Annual Review of Immunology 2012 30 531 564 2-s2.0-84859416933 10.1146/annurev.immunol.25.022106.141623
35. Lühder F., Höglund P., Allison J. P., Benoist C., Mathis D., Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates the unfolding of autoimmune diabetes. The Journal of Experimental Medicine 1998 187 3 427 432 2-s2.0-2642655282 10.1084/jem.187.3.427
36. Khattri R., Auger J. A., Griffin M. D., Sharpe A. H., Bluestone J. A., Lymphoproliferative disorder in CTLA-4 knockout mice is characterized by CD28-regulated activation of Th2 responses. The Journal of Immunology 1999 162 10 5784 5791 2-s2.0-0033563265
37. Łuczyński W., Wawrusiewicz-Kurylonek N., Stasiak-Barmuta A., Urban R., Iłendo E., Urban M., Hryszko M., Kretowski A., Górska M., Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes. Acta Biochimica Polonica 2009 56 2 361 370 2-s2.0-68249100526
38. Araki M., Chung D., Liu S., Rainbow D. B., Chamberlain G., Garner V., Hunter K. M. D., Vijayakrishnan L., Peterson L. B., Oukka M., Sharpe A. H., Sobel R., Kuchroo V. K., Wicker L. S., 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. The Journal of Immunology 2009 183 8 5146 5157 2-s2.0-77954092701 10.4049/jimmunol.0802610
39. Shieh S.-J., Chou F.-C., Yu P.-N., Lin W.-C., Chang D.-M., Roffler S. R., Sytwu H.-K., Transgenic expression of single-chain anti-CTLA-4 Fv on β cells protects nonobese diabetic mice from autoimmune diabetes. The Journal of Immunology 2009 183 4 2277 2285 2-s2.0-70149123492 10.4049/jimmunol.0900679
40. Lundholm M., Motta V., Löfgren-Burström A., Duarte N., Bergman M.-L., Mayans S., Holmberg D., Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1. Diabetes 2006 55 2 538 544 2-s2.0-33644753940 10.2337/diabetes.55.02.06.db05-1240
41. Dose-effect relationship of low-dose IL-2 in type 1 diabetes. http://clinicaltrials.gov/ct2/show/NCT01353833
42. Home-gene-ncbi. June 2013, http://www.ncbi.nlm.nih.gov/gene/
43. Martin S., Wolf-Eichbaum D., Duinkerken G., Scherbaum W. A., Kolb H., Noordzij J. G., Roep B. O., Development of type 1 diabetes despite severe hereditary B-cell deficiency. The New England Journal of Medicine 2001 345 14 1036 1040 2-s2.0-0035807589 10.1056/NEJMoa010465
44. Xiu Y., Wong C. P., Bouaziz J.-D., Hamaguchi Y., Wang Y., Pop S. M., Tisch R. M., Tedder T. F., B lymphocyte depletion by CD20 monoclonal antibody prevents diabetes in nonobese diabetic mice despite isotype-specific differences in Fc γ R effector functions. The Journal of Immunology 2008 180 5 2863 2875 2-s2.0-43049171493
45. Smith S. H., Tedder T. F., Targeting B-cells mitigates autoimmune diabetes in NOD mice: what is plan b? Diabetes 2009 58 7 1479 1481 2-s2.0-67650251671 10.2337/db09-0497
46. Thien M., Phan T. G., Gardam S., Amesbury M., Basten A., MacKay F., Brink R., Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity 2004 20 6 785 798 2-s2.0-2942518502 10.1016/j.immuni.2004.05.010
47. 10 cells inhibit intestinal injury in a mouse model. The American Journal of Pathology 2011 178 2 735 743 2-s2.0-79951825006 10.1016/j.ajpath.2010.10.022
48. Chen X., Jensen P. E., Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+ CD4 T cells. The Journal of Immunology 2007 179 4 2046 2050 2-s2.0-34848922720
49. Jerne N. K., Towards a network theory of the immune system. Annales d'Immunologie 1974 125C 1-2 373 389 2-s2.0-0015956495
50. Hampe C. S., Protective role of anti-idiotypic antibodies in autoimmunity-lessons for type 1 diabetes. Autoimmunity 2012 45 4 320 331 2-s2.0-84859835474 10.3109/08916934.2012.659299
51. Brown J. C., Rodkey L. S., Autoregulation of an antibody response via network-induced auto-anti-idiotype. The Journal of Experimental Medicine 1979 150 1 67 85 2-s2.0-0018744650
52. Scaglia L., Cahill C. J., Finegood D. T., Bonner-Weir S., Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinology 1997 138 4 1736 1741 2-s2.0-0030903840 10.1210/en.138.4.1736
53. Trudeau J. D., Dutz J. P., Arany E., Hill D. J., Fieldus W. E., Finegood D. T., Neonatal β -cell apoptosis: a trigger for autoimmune diabetes? Diabetes 2000 49 1 1 7 2-s2.0-0033985277
54. Kassem S. A., Ariel I., Thornton P. S., Scheimberg I., Glaser B., β -Cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Diabetes 2000 49 8 1325 1333 2-s2.0-0033853921
55. Höglund P., Mintern J., Waltzinger C., Heath W., Benoist C., Mathis D., Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. The Journal of Experimental Medicine 1999 189 2 331 339 2-s2.0-0033579875 10.1084/jem.189.2.331
56. O'Brien B. A., Huang Y., Geng X., Dutz J. P., Finegood D. T., Phagocytosis of apoptotic cells by macrophages from NOD mice is reduced. Diabetes 2002 51 8 2481 2488 2-s2.0-0036320896
57. Kim H. S., Han M. S., Chung K. W., Kim S., Kim E., Kim M. J., Jang E., Lee H. A., Youn J., Akira S., Lee M.-S., Toll-like receptor 2 senses β -cell death and contributes to the initiation of autoimmune diabetes. Immunity 2007 27 2 321 333 2-s2.0-34548036686 10.1016/j.immuni.2007.06.010
58. Jun H.-S., Yoon C.-S., Zbytnuik L., van Rooijen N., Yoon J.-W., The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice. The Journal of Experimental Medicine 1999 189 2 347 358 2-s2.0-0033579877 10.1084/jem.189.2.347
59. Carrington E. M., Kos C., Zhan Y., Krishnamurthy B., Allison J., Reducing or increasing β -cell apoptosis without inflammation does not affect diabetes initiation in neonatal NOD mice. European Journal of Immunology 2011 41 8 2238 2247 2-s2.0-79960724246 10.1002/eji.201141476
60. Byrne J. C., Ní Gabhann J., Lazzari E., Genetics of SLE: functional relevance for monocytes/macrophages in disease. Clinical and Developmental Immunology 2012 2012 15 10.1155/2012/582352 582352
61. Sabioncello A., Rabatic S., Kadrnka-Lovrencic M., Decreased phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) in type-1 diabetes. Biomedicine 1981 35 7-8 227 229 2-s2.0-0019718714
62. Espinoza-Jiménez A., Peón A. N., Terrazas L. I., Alternatively activated macrophages in types 1 and 2 diabetes. Mediators of Inflammation 2012 2012 10 10.1155/2012/815953
63. Lee M.-S., Kwon H.-J., Kim H. S., Macrophages from nonobese diabetic mouse have a selective defect in IFN- γ but not IFN- α / β receptor pathway. Journal of Clinical Immunology 2012 23 4 753 761 2-s2.0-84857669680 10.1007/s10875-012-9682-3
64. Dalton D. K., Pitts-Meek S., Keshav S., Figari I. S., Bradley A., Stewart T. A., Multiple defects of immune cell function in mice with disrupted interferon- γ genes. Science 1993 259 5102 1739 1742 2-s2.0-0027400726
65. Turley S., Poirot L., Hattori M., Benoist C., Mathis D., Physiological β cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. The Journal of Experimental Medicine 2003 198 10 1527 1537 2-s2.0-0345448056 10.1084/jem.20030966
66. Danke N. A., Koelle D. M., Yee C., Beheray S., Kwok W. W., Autoreactive T cells in healthy individuals. The Journal of Immunology 2004 172 10 5967 5972 2-s2.0-2442522323
67. Orban T., Farkas K., Jalahej H., Kis J., Treszl A., Falk B., Reijonen H., Wolfsdorf J., Ricker A., Matthews J. B., Tchao N., Sayre P., Bianchine P., Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy. The Journal of Autoimmunity 2010 34 4 408 415 2-s2.0-77952243765 10.1016/j.jaut.2009.10.005
68. Hugues S., Mougneau E., Ferlin W., Jeske D., Hofman P., Homann D., Beaudoin L., Schrike C., von Herrath M., Lehuen A., Glaichenhaus N., Tolerance to islet antigens and prevention from diabetes induced by limited apoptosis of pancreatic β cells. Immunity 2002 16 2 169 181 2-s2.0-18344370780 10.1016/S1074-7613(02)00273-X
69. Rayat G. R., Rajotte R. V., Lyon J. G., Dufour J. M., Hacquoil B. V., Korbutt G. S., Immunization with streptozotocin-treated NOD mouse islets inhibits the onset of autoimmune diabetes in NOD mice. The Journal of Autoimmunity 2003 21 1 11 15 2-s2.0-0038782328 10.1016/S0896-8411(03)00080-5
70. Gonzalez A., Andre-Schmutz I., Carnaud C., Mathis D., Benoist C., Damage control, rather than unresponsiveness, effected by protective DX5+ T cells in autoimmune diabetes. Nature Immunology 2001 2 12 1117 1125 2-s2.0-0035198718 10.1038/ni738
71. Lee M.-S., Mueller R., Wicker L. S., Peterson L. B., Sarvetnick N., IL-10 is necessary and sufficient for autoimmune diabetes in conjunction with NOD MHC homozygosity. The Journal of Experimental Medicine 1996 183 6 2663 2668 2-s2.0-0029896602 10.1084/jem.183.6.2663
72. Mak T. W., Saunders M., The Immune Response: Basic and Clinical Principles 2005 Academic Press
73. Rock K. L., Hearn A., Chen C.-J., Shi Y., Natural endogenous adjuvants. Springer Seminars in Immunopathology 2005 26 3 231 246 2-s2.0-12444252115 10.1007/s00281-004-0173-3
74. Dresser D. W., Specific inhibition of antibody production. II. Paralysis induced in adult mice by small quantities of protein antigen. Immunology 1962 5 3 378 388 2-s2.0-0000017699
75. Claman H. N., Tolerance to a protein antigen in adult mice and the effect of nonspecific factors. The Journal of Immunology 1963 91 833 839 2-s2.0-0642282753
76. Bretscher P., Cohn M., A theory of self-nonself discrimination. Science 1970 169 3950 1042 1049 2-s2.0-0014941813
77. Rosenstreich D. L., Mizel S. B., Signal requirements for T lymphocyte activation. I. Replacement of macrophage function with phorbol myristic acetate. The Journal of Immunology 1979 123 4 1749 1754 2-s2.0-0018710572
78. Quill H., Schwartz R. H., Stimulation of normal inducer T cell clones with antigen presented by purified Ia molecules in planar lipid membranes: specific induction of a long-lived state of proliferative nonresponsiveness. The Journal of Immunology 1987 138 11 3704 3712 2-s2.0-0023266396
79. Kono H., Rock K. L., How dying cells alert the immune system to danger. Nature Reviews Immunology 2008 8 4 279 289 2-s2.0-41149118513 10.1038/nri2215
80. Finberg R. W., Wang J. P., Kurt-Jones E. A., Toll like receptors and viruses. Reviews in Medical Virology 2007 17 1 35 43 2-s2.0-33846331649 10.1002/rmv.525
81. Hallman M., Rämet M., Ezekowitz R. A., Toll-like receptors as sensors of pathogens. Pediatric Research 2001 50 3 315 321 2-s2.0-0034868267
82. Shi Y., Zheng W., Rock K. L., Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses. Proceedings of the National Academy of Sciences of the United States of America 2000 97 26 14590 14595 2-s2.0-0034687696 10.1073/pnas.260497597
83. Bellone M., Iezzi G., Rovere P., Galati G., Ronchetti A., Protti M. P., Davoust J., Rugarli C., Manfredi A. A., Processing of engulfed apoptotic bodies yields T cell epitopes. The Journal of Immunology 1997 159 11 5391 5399 2-s2.0-0031297434
84. Albert M. L., Sauter B., Bhardwaj N., Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLS. Nature 1998 392 6671 86 89 2-s2.0-0032485487 10.1038/32183
85. Inaba K., Turley S., Yamaide F., Iyoda T., Mahnke K., Inaba M., Pack M., Subklewe M., Sauter B., Sheff D., Albert M., Bhardwaj N., Mellman I., Steinman R. M., Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. The Journal of Experimental Medicine 1998 188 11 2163 2173 2-s2.0-0031798137 10.1084/jem.188.11.2163
86. Horváth L., Cervenak L., Oroszlán M., Prohászka Z., Uray K., Hudecz F., Baranyi É., Madácsy L., Singh M., Romics L., Füst G., Pánczél P., Antibodies against different epitopes of heat-shock protein 60 in children with type 1 diabetes mellitus. Immunology Letters 2002 80 3 155 162 2-s2.0-0036498093 10.1016/S0165-2478(01)00336-4
87. Takizawa S., Endo T., Wanjia X., Tanaka S., Takahashi M., Kobayashi T., HSP 10 is a new autoantigen in both autoimmune pancreatitis and fulminant type 1 diabetes. Biochemical and Biophysical Research Communications 2009 386 1 192 196 2-s2.0-67649207580 10.1016/j.bbrc.2009.06.009
88. Shimada A., Kasatani T., Takei I., Maruyama T., Nomaguchi H., Ozawa Y., Ishii M., Kasuga A., Tashiro F., Miyazaki J.-I., Yamamura K.-I., Saruta T., Immune response to heat-shock protein correlates with induction of insulitis in I-E α d transgenic NOD mice. Diabetes 1996 45 2 165 169 2-s2.0-0030042414
89. Srivastava P. K., Maki R. G., Stress-induced proteins in immune response to cancer. Current Topics in Microbiology and Immunology 1991 167 109 123 2-s2.0-0026069595
90. Singh-Jasuja H., Scherer H. U., Hilf N., The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. European Journal of Immunology 2000 30 8 2211 2215
91. Kuppner M. C., Gastpar R., Gelwer S., The role of heat shock protein (hsp70) in dendritic cell maturation: hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors. European Journal of Immunology 2001 31 5 1602 1609
92. Asea A., Kraeft S.-K., Kurt-Jones E. A., Stevenson M. A., Chen L. B., Finberg R. W., Koo G. C., Calderwood S. K., HSP70 stimulates cytokine production through a CD 14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nature Medicine 2000 6 4 435 442 2-s2.0-0034113617 10.1038/74697
93. Gao B., Tsan M.-F., Recombinant human heat shock protein 60 does not induce the release of tumor necrosis factor α from murine macrophages. The Journal of Biological Chemistry 2003 278 25 22523 22529 2-s2.0-0037928705 10.1074/jbc.M303161200
94. Schmitt E., Gehrmann M., Brunet M., Multhoff G., Garrido C., Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. Journal of Leukocyte Biology 2007 81 1 15 27 2-s2.0-33845913216 10.1189/jlb.0306167
95. Pawaria S., Binder R. J., CD91-dependent programming of T-helper cell responses following heat shock protein immunization. Nature Communications 2011 2 1, article 521 2-s2.0-84855712718 10.1038/ncomms1524
96. Miyagawa J.-I., Miuchi M., Namba M., Incretin-based therapy in patients with type 1 diabetes mellitus. Nippon Rinsho 2011 69 5 923 929 2-s2.0-79960072387
97. Shi Y., Caught red-handed: uric acid is an agent of inflammation. The Journal of Clinical Investigation 2010 120 6 1809 1811 2-s2.0-77953181490 10.1172/JCI43132
98. Knip M., Virtanen S. M., Åkerblom H. K., Infant feeding and the risk of type 1 diabetes. The American Journal of Clinical Nutrition 2010 91 5 1506S 1513S 2-s2.0-77951965439 10.3945/ajcn.2010.28701C
99. Coppieters K. T., Boettler T., von Herrath M., Virus infections in type 1 diabetes. Cold Spring Harbor Perspectives in Medicine 2012 2 1, article a007682 10.1101/cshperspect.a007682
100. Gamble D. R., Kinsley M. L., FitzGerald M. G., Bolton R., Taylor K. W., Viral antibodies in diabetes mellitus. British Medical Journal 1969 3 5671 627 630 2-s2.0-0014673558
101. Clements G. B., Galbraith D. N., Taylor K. W., Coxsackie B virus infection and onset of childhood diabetes. Lancet 1995 346 8969 221 223 2-s2.0-0029034877
102. Shimada A., Maruyama T., Encephalomyocarditis-virus-induced diabetes model resembles 'fulminant' type 1 diabetes in humans. Diabetologia 2004 47 10 1854 1855 2-s2.0-11144253498 10.1007/s00125-004-1538-9
103. Schloot N. C., Willemen S. J. M., Duinkerken G., Drijfhout J. W., de Vries R. R. P., Roep B. O., Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to coxsackie or proinsulin peptides do not crossreact with homologous counterpart. Human Immunology 2001 62 4 299 309 2-s2.0-0035044922 10.1016/S0198-8859(01)00223-3
104. Sevilla N., Homann D., von Herrath M., Rodriguez F., Harkins S., Whitton J. L., Oldstone M. B. A., Virus-induced diabetes in a transgenic model: role of cross-reacting viruses and quantitation of effector T cells needed to cause disease. Journal of Virology 2000 74 7 3284 3292 2-s2.0-0034011436 10.1128/JVI.74.7.3284-3292.2000
105. Christen U., Edelmann K. H., McGavern D. B., Wolfe T., Coon B., Teague M. K., Miller S. D., Oldstone M. B. A., Von Herrath M. G., A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes. The Journal of Clinical Investigation 2004 114 9 1290 1298 2-s2.0-15244341417 10.1172/JCI200422557
106. Tracy S., Drescher K. M., Chapman N. M., Kim K.-S., Carson S. D., Pirruccello S., Lane P. H., Romero J. R., Leser J. S., Toward testing the hypothesis that group B coxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabetic mice with CVB markedly lowers diabetes incidence. Journal of Virology 2002 76 23 12097 12111 2-s2.0-0036889147 10.1128/JVI.76.23.12097-12111.2002
107. Pane J. A., Webster N. L., Graham K. L., Holloway G., Zufferey C., Coulson B. S., Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes. Diabetologia 2013 56 3 573 582
108. Vaarala O., Knip M., Paronen J., Hämäläinen A.-M., Muona P., Väätäinen M., Ilonen J., Simell O., Åkerblom H. K., Cow's milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes. Diabetes 1999 48 7 1389 1394 2-s2.0-0033032385 10.2337/diabetes.48.7.1389
109. Eizirik D. L., Colli M. L., Ortis F., The role of inflammation in insulitis and Β -cell loss in type 1 diabetes. Nature Reviews Endocrinology 2009 5 4 219 226 2-s2.0-67649364114 10.1038/nrendo.2009.21
110. Santin I., Moore F., Colli M. L., Gurzov E. N., Marselli L., Marchetti P., Eizirik D. L., PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β -cell apoptosis via regulation of the BH3-only protein bim. Diabetes 2011 60 12 3279 3288 2-s2.0-82255185820 10.2337/db11-0758
111. Walter U., Toepfer T., Dittmar K. E. J., Kretschmer K., Lauber J., Weiss S., Servos G., Lechner O., Scherbaum W. A., Bornstein S. R., Von Boehmer H., Buer J., Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes. Diabetologia 2003 46 8 1106 1114 2-s2.0-10744228962 10.1007/s00125-003-1164-y
112. Gurzov E. N., Eizirik D. L., Bcl-2 proteins in diabetes: mitochondrial pathways of β -cell death and dysfunction. Trends in Cell Biology 2011 21 7 424 431 2-s2.0-79959618962 10.1016/j.tcb.2011.03.001
113. Cunha D. A., Igoillo-Esteve M., Gurzov E. N., Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human β -cell apoptosis. Diabetes 2012 61 11 2763 2775 10.2337/db12-0123
114. Gurzov E. N., Germano C. M., Cunha D. A., Ortis F., Vanderwinden J.-M., Marchetti P., Zhang L., Eizirik D. L., p53 up-regulated modulator of apoptosis (PUMA) activation contributes to pancreatic β -cell apoptosis induced by proinflammatory cytokines and endoplasmic reticulum stress. The Journal of Biological Chemistry 2010 285 26 19910 19920 2-s2.0-77953755226 10.1074/jbc.M110.122374
115. Barthson J., Germano C. M., Moore F., Maida A., Drucker D. J., Marchetti P., Gysemans C., Mathieu C., Nuñez G., Jurisicova A., Eizirik D. L., Gurzov E. N., Cytokines tumor necrosis factor- α and interferon- γ induce pancreatic β -cell apoptosis through STAT1-mediated bim protein activation. The Journal of Biological Chemistry 2011 286 45 39632 39643 2-s2.0-80655144735 10.1074/jbc.M111.253591
116. Eizirik D. L., Sammeth M., Bouckenooghe T., Bottu G., Sisino G., Igoillo-Esteve M., Ortis F., Santin I., Colli M. L., Barthson J., Bouwens L., Hughes L., Gregory L., Lunter G., Marselli L., Marchetti P., McCarthy M. I., Cnop M., The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines. PLoS Genetics 2012 8 3, article e1002552 2-s2.0-84859254586 10.1371/journal.pgen.1002552
117. Yamada Y., Okubo Y., Shimada A., Oikawa Y., Yamada S., Narumi S., Matsushima K., Itoh H., Acceleration of diabetes development in CXC chemokine receptor 3 (CXCR3)-deficient NOD mice. Diabetologia 2012 55 8 2238 2245 2-s2.0-84859385048 10.1007/s00125-012-2547-8
118. Frigerio S., Junt T., Lu B., Gerard C., Zumsteg U., Holländer G. A., Piali L., β cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Nature Medicine 2002 8 12 1414 1420 2-s2.0-0036913215 10.1038/nm792
119. Christen U., McGavern D. B., Luster A. D., von Herrath M. G., Oldstone M. B. A., Among CXCR3 chemokines, IFN- γ -inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN- γ (CXCL9) imprints a pattern for the subsequent development of autoimmune disease. The Journal of Immunology 2003 171 12 6838 6845 2-s2.0-0346366978
120. Steck A. K., Armstrong T. K., Babu S. R., Eisenbarth G. S., Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes 2011 60 3 1045 1049 2-s2.0-79952384694 10.2337/db10-1419
121. Jacovetti C., Abderrahmani A., Parnaud G., MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity. The Journal of Clinical Investigation 2012 122 10 3541 3551 10.1172/JCI64151
122. Lu Q., The critical importance of epigenetics in autoimmunity. The Journal of Autoimmunity 2013 41 1 5 10.1016/j.jaut.2013.01.010
123. Toker A., Engelbert D., Garg G., Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. The The Journal of Immunology 2013 190 7 3180 3188 10.4049/jimmunol.1203473
124. Shanmugam M. K., Sethi G., Role of epigenetics in inflammation-associated diseases. Subcellular Biochemistry 2012 61 627 657
125. Akirav E. M., Lebastchi J., Galvan E. M., Henegariu O., Akirav M., Ablamunits V., Lizardi P. M., Herold K. C., Detection of β cell death in diabetes using differentially methylated circulating DNA. Proceedings of the National Academy of Sciences of the United States of America 2011 108 47 19018 19023 2-s2.0-82755197361 10.1073/pnas.1111008108
126. Miao F., Smith D. D., Zhang L., Min A., Feng W., Natarajan R., Lymphocytes from patients with type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation an epigenetic study in diabetes. Diabetes 2008 57 12 3189 3198 2-s2.0-58149345088 10.2337/db08-0645
127. Miao F., Chen Z., Zhang L., Profiles of epigenetic histone post-translational modifications at type 1 diabetes susceptible genes. The Journal of Biological Chemistry 2012 287 20 16335 16345 10.1074/jbc.M111.330373
128. Xu Z., Lefevre G. M., Felsenfeld G., Chromatin structure, epigenetic mechanisms and long-range interactions in the human insulin locus. Diabetes, Obesity and Metabolism 2012 14 supplement 3 1 11
129. Hezova R., Slaby O., Faltejskova P., Mikulkova Z., Buresova I., Raja K. R. M., Hodek J., Ovesna J., Michalek J., microRNA-342, microRNA-191 and microRNA-510 are differentially expressed in T regulatory cells of type 1 diabetic patients. Cellular Immunology 2010 260 2 70 74 2-s2.0-71349083569 10.1016/j.cellimm.2009.10.012
130. Lu L.-F., Boldin M. P., Chaudhry A., Lin L.-L., Taganov K. D., Hanada T., Yoshimura A., Baltimore D., Rudensky A. Y., Function of miR-146a in controlling treg cell-mediated regulation of Th1 responses. Cell 2010 142 6 914 929 2-s2.0-77956632634 10.1016/j.cell.2010.08.012
131. Guttman M., Donaghey J., Carey B. W., Garber M., Grenier J. K., Munson G., Young G., Lucas A. B., Ach R., Bruhn L., Yang X., Amit I., Meissner A., Regev A., Rinn J. L., Root D. E., Lander E. S., LincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 2011 477 7364 295 300 2-s2.0-80052869283 10.1038/nature10398
132. Ørom U. A., Shiekhattar R., Noncoding RNAs and enhancers: complications of a long-distance relationship. Trends in Genetics 2011 27 10 433 439 2-s2.0-80052815461 10.1016/j.tig.2011.06.009
133. Ørom U. A., Derrien T., Beringer M., Gumireddy K., Gardini A., Bussotti G., Lai F., Zytnicki M., Notredame C., Huang Q., Guigo R., Shiekhattar R., Long noncoding RNAs with enhancer-like function in human cells. Cell 2010 143 1 46 58 2-s2.0-77957243921 10.1016/j.cell.2010.09.001
134. Pullen T., Rutter G., An islet-specific long non-coding RNA (lncRNA) expressed from the Pdx1 locus regulates Pdx1 activity. Diabetologia 2012 55 212
135. von Herrath M. G., Fujinami R. S., Whitton J. L., Microorganisms and autoimmunity: making the barren field fertile? Nature Reviews Microbiology 2003 1 2 151 157 2-s2.0-1842613450
136. Moltchanova E. V., Schreier N., Lammi N., Karvonen M., Seasonal variation of diagnosis of type 1 diabetes mellitus in children worldwide. Diabetic Medicine 2009 26 7 673 678 2-s2.0-67649756856 10.1111/j.1464-5491.2009.02743.x
137. Gyurus E. K., Patterson C., Soltesz G., László A., Zsuzsa A., Márta B., László B., Bea B., Dezso B., László B., Zsuzsa B., Mária B., Violetta C., Ágnes C., Magdolna D., Miklós D., Andrea B., Éva E., Anna F. G., Eniko F., Veronika G., Éva G., Éva G., Béla G., Erzsébet G., Éva G., Éva H., Anna J., Katalin H. N., Mária H., György K., Zsuzsa K., Irén K., Edit K., János K., Károly K., Katalin K., Adrienne K., Judit K., Anna K., Kálmán K., Éva L., Andrea L., László M., Ágnes M., Mária M., Mária N., Tamás N., István P., Mária R., Tamás R., Ilona R., Ferenc R., Edit S., Gyula S., Andrea S., Hajnalka S., Zsolt S., Rozália S., Ildikó S., László S., Péter S., Margit T., Judit T., Péter T., Tamás T., Erzsébet U., Twenty-one years of prospective incidence of childhood type 1 diabetes in Hungary-the rising trend continues (or peaks and highlands?). Pediatric Diabetes 2012 13 1 21 25 2-s2.0-84856407316 10.1111/j.1399-5448.2011.00826.x
138. Bruno G., Landi A., Epidemiology and costs of diabetes. Transplantation Proceedings 2011 43 1 327 329 2-s2.0-79951782863 10.1016/j.transproceed.2010.09. 098
139. Wills-Karp M., Santeliz J., Karp C. L., The germless theory of allergic disease: revisiting the hygiene hypothesis. Nature Reviews Immunology 2001 1 1 69 75 2-s2.0-0035495857
140. Dabelea D., Pihoker C., Talton J. W., D'Agostino R. B. Jr., Fujimoto W., Klingensmith G. J., Lawrence J. M., Linder B., Marcovina S. M., Mayer-Davis E. J., Imperatore G., Dolan L. M., SEARCH for Diabetes in Youth Study S. F. D. I. Y. S., Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes Care 2011 34 7 1628 1633 2-s2.0-80054692680
141. Clemente-Casares X., Tsai S., Huang C., Santamaria P., Antigen-specific therapeutic approaches in type 1 diabetes. Cold Spring Harbor Perspectives in Medicine 2012 2 2, article a007773
142. Li X., Liao L., Yan X., Huang G., Lin J., Lei M., Wang X., Zhou Z., Protective effects of 1- α -hydroxyvitamin D3 on residual β -cell function in patients with adult-onset latent autoimmune diabetes (LADA). Diabetes/Metabolism Research and Reviews 2009 25 5 411 416 2-s2.0-70350680951 10.1002/dmrr.977
143. Walter M., Kaupper T., Adler K., Foersch J., Bonifacio E., Ziegler A.-G., No effect of the 1 α25-dihydroxyvitamin D3 on β -cell residual function and insulin requirement in adults with new-onset type 1 diabetes. Diabetes Care 2010 33 7 1443 1448 2-s2.0-77956263961 10.2337/dc09-2297
144. Munger K. L., Levin L. I., Massa J., Horst R., Orban T., Ascherio A., Preclinical serum 25-hydroxyvitamin D levels and risk of type 1 diabetes in a cohort of US military personnel. American Journal of Epidemiology 2013 177 5 411 419
145. Varga T., Somogyi A., Barna G., Wichmann B., Nagy G., Rácz K., Selmeci L., Firneisz G., Higher serum DPP-4 enzyme activity and decreased lymphocyte CD26 expression in type 1 diabetes. Pathology and Oncology Research 2011 17 4 925 930 2-s2.0-84855435744 10.1007/s12253-011-9404-9
146. Hadjiyanni I., Siminovitch K. A., Danska J. S., Drucker D. J., Glucagon-like peptide-1 receptor signalling selectively regulates murine lymphocyte proliferation and maintenance of peripheral regulatory T cells. Diabetologia 2010 53 4 730 740 2-s2.0-77949268923 10.1007/s00125-009-1643-x
147. Ellis S. L., Moser E. G., Snell-Bergeon J. K., Rodionova A. S., Hazenfield R. M., Garg S. K., Effect of sitagliptin on glucose control in adult patients with type1 diabetes: a pilot, double-blind, randomized, crossover trial. Diabetic Medicine 2011 28 10 1176 1181 2-s2.0-80053003537 10.1111/j.1464-5491.2011.03331.x
148. Kielgast U., Krarup T., Holst J. J., Madsbad S., Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diabetes care 2011 34 7 1463 1468 2-s2.0-80054690193
149. Miller R. G., Secrest A. M., Sharma R. K., Songer T. J., Orchard T. J., Improvements in the life expectancy of type 1 diabetes the Pittsburgh Epidemiology of Diabetes Complications Study Cohort. Diabetes 2012 61 11 2987 2992