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Glisic S, Jailwala P. Interaction between Treg apoptosis pathways, Treg function and HLA risk evolves during type 1 diabetes pathogenesis. PLoS One. 2012;7(4):e36040doi: 10.1371/journal.pone.0036040.
Glisic, S., & Jailwala, P. (2012). Interaction between Treg apoptosis pathways, Treg function and HLA risk evolves during type 1 diabetes pathogenesis. PloS one, 7(4), e36040. https://doi.org/10.1371/journal.pone.0036040
Glisic, Sanja, and Jailwala, Parthav. "Interaction between Treg apoptosis pathways, Treg function and HLA risk evolves during type 1 diabetes pathogenesis." PloS one vol. 7,4 (2012): e36040. doi: https://doi.org/10.1371/journal.pone.0036040
Glisic S, Jailwala P. Interaction between Treg apoptosis pathways, Treg function and HLA risk evolves during type 1 diabetes pathogenesis. PLoS One. 2012;7(4):e36040. doi: 10.1371/journal.pone.0036040. Epub 2012 Apr 26. PMID: 22563437; PMCID: PMC3338571.
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PLoS One. 2012;7(4):e36040. doi: 10.1371/journal.pone.0036040. Epub 2012 Apr 26.

Interaction between Treg apoptosis pathways, Treg function and HLA risk evolves during type 1 diabetes pathogenesis.

PloS one

Sanja Glisic, Parthav Jailwala

Affiliations

  1. Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America. [email protected]

PMID: 22563437 PMCID: PMC3338571 DOI: 10.1371/journal.pone.0036040

Abstract

We have previously reported increased apoptosis of regulatory T cells (Tregs) in recent-onset Type 1 Diabetes subjects (RO T1D) in the honeymoon phase and in multiple autoantibody-positive (Ab+) subjects, some of which are developing T1D. We have also reported that increased Treg apoptosis was associated with High HLA risk and that it subsided with cessation of honeymoon period. In this report, we present results generated using genetics, genomics, functional cell-based assays and flow cytometry to assess cellular changes at the T-cell level during T1D pathogenesis. We measured ex vivo Treg apoptosis and Treg function, surface markers expression, expression of HLA class II genes, the influence of HLA risk on Treg apoptosis and function, and evaluated contribution of genes reported to be involved in the apoptosis process. This integrated comprehensive approach uncovered important information that can serve as a basis for future studies aimed to modulate Treg cell responsiveness to apoptotic signals in autoimmunity. For example, T1D will progress in those subjects where increased Treg apoptosis is accompanied with decreased Treg function. Furthermore, Tregs from High HLA risk healthy controls had increased Treg apoptosis levels and overexpressed FADD but not Fas/FasL. Tregs from RO T1D subjects in the honeymoon phase were primarily dying through withdrawal of growth hormones with contribution of oxidative stress, mitochondrial apoptotic pathways, and employment of TNF-receptor family members. Ab+ subjects, however, expressed high inflammation level, which probably contributed to Treg apoptosis, although other apoptotic pathways were also activated: withdrawal of growth hormones, oxidative stress, mitochondrial apoptosis and Fas/FasL apoptotic pathways. The value of these results lie in potentially different preventive treatment subjects would receive depending on disease progression stage when treated.

References

  1. Mol Cell Biol. 2004 Jul;24(13):5914-22 - PubMed
  2. Genes Immun. 2004 Aug;5(5):405-16 - PubMed
  3. Nat Genet. 2005 May;37(5):486-94 - PubMed
  4. Lab Invest. 2010 Dec;90(12):1747-56 - PubMed
  5. Cell Immunol. 1992 Jan;139(1):268-73 - PubMed
  6. J Immunol. 1991 Aug 1;147(3):774-80 - PubMed
  7. JAMA. 2007 Jun 27;297(24):2716-24 - PubMed
  8. Cell. 2006 Jul 28;126(2):375-87 - PubMed
  9. J Immunol. 1989 Jul 15;143(2):762-9 - PubMed
  10. Am J Hum Genet. 1996 Nov;59(5):1134-48 - PubMed
  11. Recent Prog Horm Res. 2001;56:69-89 - PubMed
  12. Diabetologia. 1999 Dec;42(12):1395-403 - PubMed
  13. J Autoimmun. 2002 Feb;18(1):67-70 - PubMed
  14. Hum Immunol. 1987 Sep;20(1):59-70 - PubMed
  15. J Immunol. 1990 Oct 1;145(7):2070-6 - PubMed
  16. Clin Exp Immunol. 2003 Sep;133(3):476-84 - PubMed
  17. Science. 2000 Jan 28;287(5453):664-6 - PubMed
  18. Mol Biol Cell. 2006 May;17(5):2150-7 - PubMed
  19. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14559-63 - PubMed
  20. Diabetologia. 1993 May;36(5):371-7 - PubMed
  21. N Engl J Med. 1990 Jun 28;322(26):1836-41 - PubMed
  22. Cell Immunol. 1999 Feb 25;192(1):79-85 - PubMed
  23. Cell. 2006 Feb 10;124(3):587-99 - PubMed
  24. Autoimmunity. 2008 Feb;41(1):11-8 - PubMed
  25. Eur J Immunol. 1994 Jan;24(1):71-5 - PubMed
  26. Hum Mol Genet. 2001 Sep 15;10(19):2025-37 - PubMed
  27. Annu Rev Immunol. 1990;8:681-715 - PubMed
  28. Immunogenetics. 1997;45(3):163-70 - PubMed
  29. J Immunol. 1991 Dec 15;147(12):4094-102 - PubMed
  30. Int J Biochem Cell Biol. 2007;39(1):44-84 - PubMed
  31. Genes Immun. 2002 Aug;3(5):235-49 - PubMed
  32. Am J Hum Genet. 1999 Mar;64(3):793-800 - PubMed
  33. Diabetes. 1991 Apr;40(4):478-81 - PubMed
  34. Lancet. 1974 Oct 12;2(7885):864-6 - PubMed
  35. J Immunol. 2001 Feb 1;166(3):1482-91 - PubMed
  36. Nat Med. 2005 Jul;11(7):757-64 - PubMed
  37. Am J Respir Cell Mol Biol. 2011 Jun;44(6):879-87 - PubMed
  38. Immunol Today. 1996 Jul;17(7):323-9 - PubMed
  39. Plant Physiol. 2006 Jun;141(2):357-66 - PubMed
  40. Nature. 1987 Oct 15-21;329(6140):599-604 - PubMed
  41. Free Radic Biol Med. 2011 Mar 1;50(5):567-75 - PubMed
  42. Curr Top Microbiol Immunol. 1990;164:17-40 - PubMed
  43. Kidney Int. 2006 Aug;70(4):724-31 - PubMed
  44. FASEB J. 2002 Nov;16(13):1738-48 - PubMed
  45. J Immunol. 2006 Apr 15;176(8):4622-31 - PubMed
  46. Oncol Rep. 2011 Aug;26(2):359-69 - PubMed
  47. Verh K Acad Geneeskd Belg. 1996;58(5):539-86 - PubMed
  48. J Immunol. 1998 Dec 1;161(11):6113-21 - PubMed
  49. Diabetes. 2000 Dec;49(12):2217-21 - PubMed
  50. J Exp Med. 1996 Mar 1;183(3):1253-8 - PubMed
  51. J Biol Chem. 2003 Aug 22;278(34):31941-9 - PubMed
  52. Endocr Rev. 2008 Feb;29(1):42-61 - PubMed
  53. J Immunol. 2005 Jul 1;175(1):32-6 - PubMed
  54. Eur J Immunogenet. 2002 Aug;29(4):321-30 - PubMed
  55. Clin Genet. 1984 Dec;26(6):529-42 - PubMed
  56. Nouv Rev Fr Hematol. 1990;32(5):333-5 - PubMed
  57. J Biol Chem. 2001 Jun 8;276(23):20659-72 - PubMed
  58. PLoS One. 2009 Aug 05;4(8):e6527 - PubMed
  59. Nat Genet. 2006 Oct;38(10):1166-72 - PubMed
  60. Tissue Antigens. 2003 Oct;62(4):296-307 - PubMed
  61. Diabet Med. 1998 Jul;15(7):539-53 - PubMed
  62. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E275-81 - PubMed
  63. FASEB J. 2010 Aug;24(8):2631-40 - PubMed
  64. J Neural Transm (Vienna). 2002;109(1):1-13 - PubMed
  65. PLoS One. 2007 Jan 03;2(1):e146 - PubMed
  66. Tissue Antigens. 2005 Jan;65(1):115-9 - PubMed
  67. J Biol Chem. 2006 Feb 3;281(5):2631-8 - PubMed
  68. Genes Immun. 2009 Jun;10(4):334-40 - PubMed
  69. J Immunol. 1996 Jan 15;156(2):603-10 - PubMed
  70. Cell Death Differ. 2011 Oct;18(10):1664-74 - PubMed
  71. World J Surg. 2011 Sep;35(9):1984-92 - PubMed
  72. J Immunol. 2002 Jan 15;168(2):763-70 - PubMed
  73. Cell. 1998 Aug 21;94(4):491-501 - PubMed
  74. Diabetes Obes Metab. 2009 Feb;11 Suppl 1:2-7 - PubMed
  75. Diabetes. 1998 Aug;47(8):1177-84 - PubMed
  76. Can J Physiol Pharmacol. 2006 Jan;84(1):39-48 - PubMed

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