Display options
Cite
Rother N, van der Vlag J. Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Front Immunol. 2015;6:610doi: 10.3389/fimmu.2015.00610.
Rother, N., & van der Vlag, J. (2015). Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Frontiers in immunology, 6610. https://doi.org/10.3389/fimmu.2015.00610
Rother, Nils, and van der Vlag, Johan. "Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus." Frontiers in immunology vol. 6 (2015): 610. doi: https://doi.org/10.3389/fimmu.2015.00610
Rother N, van der Vlag J. Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. Front Immunol. 2015 Nov 30;6:610. doi: 10.3389/fimmu.2015.00610. eCollection 2015. PMID: 26648939; PMCID: PMC4663269.
Copy Download .nbib Format: NLM
Share it on

Front Immunol. 2015 Nov 30;6:610. doi: 10.3389/fimmu.2015.00610. eCollection 2015.

Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus.

Frontiers in immunology

Nils Rother, Johan van der Vlag

Affiliations

  1. Department of Nephrology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences , Nijmegen , Netherlands.

PMID: 26648939 PMCID: PMC4663269 DOI: 10.3389/fimmu.2015.00610

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against nuclear components. Circulating immune complexes of chromatin and autoantibodies deposit in various tissues leading to inflammation and tissue damage. It has been well documented that autoimmunity in SLE depends on autoreactive T cells. In this review, we summarize the literature that addresses the roles of T cell signaling, and Th17 and regulatory T cells (Tregs) in the development of SLE. T cell receptor (TCR) signaling appears to be aberrant in T cells of patients with SLE. In particular, defects in the TCRζ chain, Syk kinase, and calcium signaling molecules have been associated with SLE, which leads to hyperresponsive autoreactive T cells. Furthermore, in patients with SLE increased numbers of autoreactive Th17 cells have been documented, and Th17 cells appear to be responsible for tissue inflammation and damage. In addition, reduced numbers of Tregs as well as Tregs with an impaired regulatory function have been associated with SLE. The altered balance between the number of Tregs and Th17 cells in SLE may result from changes in the cytokine milieu that favors the development of Th17 cells over Tregs.

Keywords: T cells; TCR signaling; Th17 cells; Tregs; autoimmunity; systemic lupus erythematosus

References

  1. Arthritis Rheum. 2009 May;60(5):1472-83 - PubMed
  2. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1787-92 - PubMed
  3. Nat Rev Immunol. 2003 Dec;3(12):939-51 - PubMed
  4. Nature. 2011 Apr 28;472(7344):491-4 - PubMed
  5. Science. 1998 Dec 18;282(5397):2263-6 - PubMed
  6. J Immunol. 2000 Dec 1;165(11):6627-34 - PubMed
  7. Arthritis Rheum. 2010 Feb;62(2):542-52 - PubMed
  8. Immunity. 2007 Aug;27(2):334-48 - PubMed
  9. J Biol Chem. 2005 May 13;280(19):18959-66 - PubMed
  10. Arthritis Rheum. 2011 Jul;63(7):2058-66 - PubMed
  11. Arthritis Rheumatol. 2016 Feb;68(2):462-72 - PubMed
  12. Ann Rheum Dis. 2011 Jan;70(1):201-7 - PubMed
  13. Immunity. 2006 Feb;24(2):179-89 - PubMed
  14. Clin Immunol. 2015 Jun;158(2):221-30 - PubMed
  15. Curr Opin Rheumatol. 2008 Sep;20(5):519-25 - PubMed
  16. J Immunol. 2007 Feb 1;178(3):1960-6 - PubMed
  17. Arthritis Res Ther. 2015 Apr 16;17:103 - PubMed
  18. Curr Opin Immunol. 2008 Jun;20(3):250-8 - PubMed
  19. Eur J Immunol. 2012 Sep;42(9):2274-84 - PubMed
  20. J Exp Med. 1993 May 1;177(5):1367-81 - PubMed
  21. Arthritis Rheum. 2007 Jun;56(6):1921-33 - PubMed
  22. Cytokine. 2015 Apr;72(2):146-53 - PubMed
  23. N Engl J Med. 2011 Dec 1;365(22):2110-21 - PubMed
  24. J Biol Chem. 2012 Nov 2;287(45):38168-77 - PubMed
  25. Nature. 2004 Aug 5;430(7000):694-9 - PubMed
  26. EMBO Rep. 2007 Dec;8(12):1142-8 - PubMed
  27. J Immunol. 2007 Feb 15;178(4):2579-88 - PubMed
  28. J Immunol. 2010 Dec 1;185(11):6563-71 - PubMed
  29. J Immunol. 2007 Jun 1;178(11):6876-85 - PubMed
  30. PLoS One. 2013 Jun 24;8(6):e67003 - PubMed
  31. Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1281-5 - PubMed
  32. Blood. 2009 Apr 30;113(18):4240-9 - PubMed
  33. Inflammation. 2013 Dec;36(6):1424-30 - PubMed
  34. Blood. 2008 Sep 1;112(5):2101-10 - PubMed
  35. Arthritis Rheum. 2010 Jul;62(7):2086-92 - PubMed
  36. J Clin Invest. 2010 Sep;120(9):3280-95 - PubMed
  37. Arthritis Rheum. 2011 Feb;63(2):523-9 - PubMed
  38. Nat Immunol. 2005 Dec;6(12):1253-62 - PubMed
  39. Arthritis Rheum. 2012 Mar;64(3):799-807 - PubMed
  40. Arthritis Rheum. 2011 Sep;63(9):2755-63 - PubMed
  41. J Immunol. 2005 Dec 15;175(12):8392-400 - PubMed
  42. Arthritis Rheum. 2010 May;62(5):1431-7 - PubMed
  43. J Immunol. 2010 Aug 15;185(4):2295-305 - PubMed
  44. Eur J Immunol. 2010 Feb;40(2):569-78 - PubMed
  45. Clin Immunol. 2004 Jan;110(1):55-62 - PubMed
  46. Eur J Immunol. 2008 Dec;38(12):3274-81 - PubMed
  47. Nat Rev Rheumatol. 2010 Jun;6(6):317-25 - PubMed
  48. Blood. 2008 Sep 15;112(6):2340-52 - PubMed
  49. PLoS One. 2013 Aug 27;8(8):e74550 - PubMed
  50. J Immunol. 2008 Dec 15;181(12):8761-6 - PubMed
  51. Annu Rev Immunol. 2008;26:453-79 - PubMed
  52. J Exp Med. 2005 Jan 17;201(2):233-40 - PubMed
  53. PLoS One. 2013;8(4):e60646 - PubMed
  54. Nat Immunol. 2005 Nov;6(11):1142-51 - PubMed
  55. Clin Exp Immunol. 2002 Jul;129(1):160-8 - PubMed
  56. Cell. 1992 Nov 13;71(4):649-62 - PubMed
  57. Clin Dev Immunol. 2012;2012:823085 - PubMed
  58. Nature. 2013 Apr 25;496(7446):513-7 - PubMed
  59. Annu Rev Immunol. 2002;20:371-94 - PubMed
  60. J Biol Chem. 2012 Apr 6;287(15):11833-41 - PubMed
  61. Arthritis Rheum. 2008 Mar;58(3):801-12 - PubMed
  62. Nat Genet. 2008 Sep;40(9):1059-61 - PubMed
  63. Clin Immunol. 2003 Jan;106(1):41-9 - PubMed
  64. J Clin Invest. 2005 Apr;115(4):996-1005 - PubMed
  65. Nat Med. 2012 Jun 06;18(6):871-82 - PubMed
  66. Lupus. 2008 Apr;17(4):289-94 - PubMed
  67. J Immunol. 2012 Feb 1;188(3):1206-12 - PubMed
  68. Science. 1995 Jun 9;268(5216):1472-6 - PubMed
  69. Ann Rheum Dis. 2012 Apr;71 Suppl 2:i78-81 - PubMed
  70. Clin Dev Immunol. 2013;2013:985753 - PubMed
  71. Immunity. 2008 Jul 18;29(1):44-56 - PubMed
  72. N Engl J Med. 2003 Oct 16;349(16):1526-33 - PubMed
  73. Arthritis Res Ther. 2010;12 Suppl 1:S3 - PubMed
  74. Lupus. 2000;9(8):589-93 - PubMed
  75. Autoimmunity. 2007 Feb;40(1):1-8 - PubMed
  76. J Clin Invest. 2005 Nov;115(11):3193-204 - PubMed
  77. J Immunol. 2003 Sep 1;171(5):2496-503 - PubMed
  78. Front Immunol. 2012 Nov 23;3:352 - PubMed
  79. J Autoimmun. 2006 Sep;27(2):110-8 - PubMed
  80. Lupus. 2008 May;17(5):371-5 - PubMed
  81. Curr Opin Rheumatol. 2011 Sep;23 (5):449-53 - PubMed
  82. Arthritis Rheum. 2008 Nov;58(11):3309-18 - PubMed
  83. Int Immunol. 2008 Jul;20(7):861-8 - PubMed
  84. Annu Rev Immunol. 2012;30:531-64 - PubMed
  85. Nat Med. 2012 Sep;18(9):1434-40 - PubMed
  86. N Engl J Med. 1979 Jul 5;301(1):5-8 - PubMed
  87. J Immunol. 2008 Dec 1;181(11):8145-52 - PubMed
  88. Nat Immunol. 2008 Feb;9(2):166-75 - PubMed
  89. Oncogene. 2001 Apr 30;20(19):2490-7 - PubMed
  90. Front Immunol. 2014 Apr 09;5:164 - PubMed
  91. J Immunol. 2011 Apr 1;186(7):4508-17 - PubMed
  92. Arthritis Rheum. 1982 Apr;25(4):401-6 - PubMed
  93. J Immunol. 2008 Jan 15;180(2):1060-70 - PubMed
  94. Clin Immunol. 2012 Mar;142(3):243-51 - PubMed
  95. Nature. 1998 Sep 3;395(6697):82-6 - PubMed
  96. J Exp Med. 2005 Oct 17;202(8):1031-6 - PubMed
  97. J Immunol. 2007 Jun 1;178(11):6725-9 - PubMed
  98. Nature. 2013 Apr 25;496(7446):518-22 - PubMed
  99. Curr Opin Immunol. 2000 Jun;12(3):242-9 - PubMed
  100. Clin Rev Allergy Immunol. 2011 Feb;40(1):42-9 - PubMed
  101. Eur J Immunol. 1995 Nov;25(11):3053-9 - PubMed
  102. Mol Immunol. 2010 Nov-Dec;48(1-3):248-56 - PubMed
  103. J Immunol. 2011 Jun 15;186(12):6693-700 - PubMed
  104. J Exp Med. 2007 Nov 26;204(12):2825-35 - PubMed

Publication Types