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Longhi MS, Mieli-Vergani G, Vergani D. Regulatory T cells in autoimmune hepatitis: an updated overview. J Autoimmun. 2021;119:102619doi: 10.1016/j.jaut.2021.102619.
Longhi, M. S., Mieli-Vergani, G., & Vergani, D. (2021). Regulatory T cells in autoimmune hepatitis: an updated overview. Journal of autoimmunity, 119102619. https://doi.org/10.1016/j.jaut.2021.102619
Longhi, Maria Serena, et al. "Regulatory T cells in autoimmune hepatitis: an updated overview." Journal of autoimmunity vol. 119 (2021): 102619. doi: https://doi.org/10.1016/j.jaut.2021.102619
Longhi MS, Mieli-Vergani G, Vergani D. Regulatory T cells in autoimmune hepatitis: an updated overview. J Autoimmun. 2021 May;119:102619. doi: 10.1016/j.jaut.2021.102619. Epub 2021 Feb 27. PMID: 33652348; PMCID: PMC8044040.
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J Autoimmun. 2021 May;119:102619. doi: 10.1016/j.jaut.2021.102619. Epub 2021 Feb 27.

Regulatory T cells in autoimmune hepatitis: an updated overview.

Journal of autoimmunity

Maria Serena Longhi, Giorgina Mieli-Vergani, Diego Vergani

Affiliations

  1. Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA. Electronic address: [email protected].
  2. Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School of Immunology & Microbial Sciences, Faculty of Liver Sciences and Medicine, King's College London, London, United Kingdom. Electronic address: [email protected].
  3. Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School of Immunology & Microbial Sciences, Faculty of Liver Sciences and Medicine, King's College London, London, United Kingdom. Electronic address: [email protected].

PMID: 33652348 PMCID: PMC8044040 DOI: 10.1016/j.jaut.2021.102619

Abstract

Regulatory T-cells (Tregs) are key players in the maintenance of immune homeostasis by preventing immune responses to self-antigens. Defects in Treg frequency and/or function result in overwhelming CD4 and CD8 T cell immune responses participating in the autoimmune attack. Perpetuation of autoimmune damage is also favored by Treg predisposition to acquire effector cell features upon exposure to a proinflammatory challenge. Treg impairment plays a permissive role in the initiation and perpetuation of autoimmune liver diseases, namely autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. In this Review, we outline studies reporting the role of Treg impairment in the pathogenesis of these conditions and discuss methods to restore Treg number and function either by generation/expansion in the test tube or through in vivo expansion upon administration of low dose IL-2. Challenges and caveats of these potential therapeutic strategies are also reviewed and discussed.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Autoimmune hepatitis; Effector lymphocytes; Immune tolerance; Immunotherapy; Regulatory T cells

References

  1. Hepatology. 2008 Feb;47(2):581-91 - PubMed
  2. Science. 2015 Aug 28;349(6251):989-93 - PubMed
  3. Immunity. 2008 Apr;28(4):546-58 - PubMed
  4. Autoimmun Rev. 2015 Feb;14(2):105-16 - PubMed
  5. Hepatology. 2001 Mar;33(3):544-53 - PubMed
  6. J Autoimmun. 2021 Feb;117:102591 - PubMed
  7. Nat Immunol. 2003 Apr;4(4):337-42 - PubMed
  8. Hepatology. 2013 Aug;58(2):718-28 - PubMed
  9. Blood. 2006 May 15;107(10):3925-32 - PubMed
  10. Nat Immunol. 2005 Dec;6(12):1219-27 - PubMed
  11. J Exp Med. 2007 Jun 11;204(6):1257-65 - PubMed
  12. J Hepatol. 2011 Feb;54(2):357-65 - PubMed
  13. Hepatology. 2015 Nov;62(5):1536-50 - PubMed
  14. Hepatology. 2011 Feb;53(2):536-47 - PubMed
  15. N Engl J Med. 1982 Nov 18;307(21):1301-4 - PubMed
  16. Ann Rheum Dis. 2019 Feb;78(2):209-217 - PubMed
  17. Nat Rev Immunol. 2020 Mar;20(3):158-172 - PubMed
  18. J Immunol. 2018 Oct 1;201(7):2094-2106 - PubMed
  19. Immunity. 2007 Oct;27(4):635-46 - PubMed
  20. J Hepatol. 2004 Jul;41(1):31-7 - PubMed
  21. Angew Chem Int Ed Engl. 2020 May 25;59(22):8425-8429 - PubMed
  22. Hepatology. 1990 Aug;12(2):224-32 - PubMed
  23. Nat Commun. 2019 May 14;10(1):2150 - PubMed
  24. J Exp Med. 2004 May 17;199(10):1401-8 - PubMed
  25. J Hepatol. 2021 Jan;74(1):48-57 - PubMed
  26. Eur J Immunol. 2000 Jun;30(6):1538-43 - PubMed
  27. Hepatology. 2014 Mar;59(3):1007-15 - PubMed
  28. Annu Rev Immunol. 2020 Apr 26;38:541-566 - PubMed
  29. J Exp Med. 2004 Jun 7;199(11):1455-65 - PubMed
  30. Gut. 1978 Apr;19(4):308-14 - PubMed
  31. J Clin Invest. 2011 Nov;121(11):4503-15 - PubMed
  32. Eur J Immunol. 2008 Jun;38(6):1654-63 - PubMed
  33. Nature. 2008 May 1;453(7191):65-71 - PubMed
  34. J Autoimmun. 2018 Nov;94:143-155 - PubMed
  35. Hepatology. 2006 Apr;43(4):729-37 - PubMed
  36. J Immunol. 2009 Feb 1;182(3):1469-80 - PubMed
  37. Front Immunol. 2017 Jan 23;8:31 - PubMed
  38. J Exp Med. 2004 Jun 7;199(11):1467-77 - PubMed
  39. Immunol Res. 2019 Feb;67(1):39-47 - PubMed
  40. Nat Med. 2007 Apr;13(4):423-31 - PubMed
  41. J Immunol. 2011 Apr 15;186(8):4734-43 - PubMed
  42. Nat Rev Immunol. 2010 Apr;10(4):236-47 - PubMed
  43. Nat Immunol. 2003 Apr;4(4):330-6 - PubMed
  44. J Immunol. 2001 Mar 15;166(6):3789-96 - PubMed
  45. Hepatology. 2009 Feb;49(2):545-52 - PubMed
  46. Clin Immunol Immunopathol. 1990 Mar;54(3):382-94 - PubMed
  47. Hepatology. 2018 Nov;68(5):1905-1921 - PubMed
  48. Immunity. 2012 Nov 16;37(5):785-99 - PubMed
  49. J Exp Med. 2006 May 15;203(5):1209-19 - PubMed
  50. Immunity. 2015 Apr 21;42(4):607-12 - PubMed
  51. Immunol Rev. 2014 May;259(1):88-102 - PubMed
  52. Eur J Immunol. 2009 Apr;39(4):1108-17 - PubMed
  53. J Immunol. 2009 Dec 1;183(11):7602-10 - PubMed
  54. J Autoimmun. 2018 Dec;95:15-25 - PubMed
  55. J Exp Med. 1996 Jun 1;183(6):2669-74 - PubMed
  56. Immunol Cell Biol. 2009 Mar-Apr;87(3):192-3 - PubMed
  57. Hepatology. 2018 Oct;68(4):1649-1652 - PubMed
  58. J Autoimmun. 2014 Sep;53:26-32 - PubMed
  59. Immunity. 2015 May 19;42(5):826-38 - PubMed
  60. Curr Opin Immunol. 2009 Jun;21(3):281-5 - PubMed
  61. Hepatology. 2006 Nov;44(5):1240-9 - PubMed
  62. J Autoimmun. 2014 May;50:123-34 - PubMed
  63. Lancet. 1976 Feb 28;1(7957):441-4 - PubMed
  64. Hepatol Commun. 2018 Feb 26;2(4):421-436 - PubMed
  65. Gastroenterology. 1986 Oct;91(4):810-7 - PubMed
  66. Nat Immunol. 2001 Apr;2(4):301-6 - PubMed
  67. Hepatology. 2009 Jan;49(1):133-40 - PubMed
  68. N Engl J Med. 2012 Dec 13;367(24):2322-33 - PubMed
  69. Nature. 2012 Mar 25;484(7395):529-33 - PubMed
  70. Nat Immunol. 2013 Apr;14(4):307-8 - PubMed
  71. Nat Immunol. 2009 Jun;10(6):595-602 - PubMed
  72. J Hepatol. 2014 May;60(5):1010-6 - PubMed
  73. Front Immunol. 2012 Jun 29;3:178 - PubMed
  74. Eur J Immunol. 2005 Oct;35(10):2886-95 - PubMed
  75. Diabetes. 2005 Jan;54(1):92-9 - PubMed
  76. J Exp Med. 1996 Aug 1;184(2):387-96 - PubMed
  77. Immunol Cell Biol. 2011 Jan;89(1):45-53 - PubMed
  78. Autoimmun Rev. 2013 Aug;12(10):972-5 - PubMed
  79. J Exp Med. 2004 Aug 2;200(3):277-85 - PubMed
  80. Immunity. 2004 Oct;21(4):589-601 - PubMed
  81. Lancet. 1984 Jun 2;1(8388):1200-4 - PubMed
  82. Immunity. 2013 Nov 14;39(5):949-62 - PubMed
  83. J Exp Med. 2004 Apr 5;199(7):971-9 - PubMed
  84. J Exp Med. 2005 Mar 7;201(5):737-46 - PubMed
  85. Clin Exp Immunol. 2009 May;156(2):217-25 - PubMed
  86. Nat Immunol. 2007 Sep;8(9):931-41 - PubMed
  87. Hepatology. 2010 Sep;52(3):999-1007 - PubMed
  88. Nature. 2008 May 1;453(7191):106-9 - PubMed
  89. Nat Immunol. 2007 Dec;8(12):1353-62 - PubMed
  90. Eur J Immunol. 2012 Jun;42(6):1375-84 - PubMed
  91. Eur J Immunol. 2005 Jun;35(6):1681-91 - PubMed
  92. Autoimmun Rev. 2018 Dec;17(12):1176-1185 - PubMed
  93. J Leukoc Biol. 2009 Oct;86(4):751-2 - PubMed
  94. Clin Exp Immunol. 2017 Jul;189(1):71-82 - PubMed
  95. J Immunol. 2005 Feb 15;174(4):1783-6 - PubMed
  96. Curr Top Microbiol Immunol. 2014;380:39-68 - PubMed
  97. Lancet. 2013 Oct 26;382(9902):1433-44 - PubMed
  98. Nat Immunol. 2005 Apr;6(4):338-44 - PubMed
  99. Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2509-14 - PubMed
  100. PLoS One. 2015 Nov 24;10(11):e0143715 - PubMed
  101. Nat Immunol. 2007 Sep;8(9):942-9 - PubMed
  102. Clin Exp Immunol. 2016 Nov;186(2):164-176 - PubMed
  103. J Autoimmun. 2015 May;59:26-37 - PubMed
  104. Cell Mol Immunol. 2010 Nov;7(6):485-90 - PubMed
  105. J Immunol. 2003 Apr 1;170(7):3631-6 - PubMed
  106. J Hepatol. 2012 Jul;57(1):125-32 - PubMed
  107. J Immunol. 1995 Aug 1;155(3):1151-64 - PubMed
  108. Cell Death Differ. 2007 Dec;14(12):2076-84 - PubMed
  109. J Clin Invest. 2003 Dec;112(11):1688-96 - PubMed
  110. J Immunol. 2006 Apr 1;176(7):4484-91 - PubMed
  111. J Exp Med. 2006 Jul 10;203(7):1701-11 - PubMed
  112. Hepatology. 2009 Jul;50(1):130-42 - PubMed
  113. J Exp Med. 2007 Jun 11;204(6):1303-10 - PubMed
  114. PLoS One. 2017 Jul 11;12(7):e0181107 - PubMed
  115. Hepatology. 2003 May;37(5):1079-85 - PubMed
  116. PLoS One. 2011 Apr 19;6(4):e18909 - PubMed
  117. JHEP Rep. 2019 Aug 21;1(4):286-296 - PubMed
  118. Nature. 2007 Nov 22;450(7169):566-9 - PubMed
  119. J Immunol. 2016 May 15;196(10):4040-51 - PubMed
  120. J Exp Med. 2001 Sep 3;194(5):629-44 - PubMed
  121. J Exp Med. 1999 Oct 4;190(7):995-1004 - PubMed
  122. Science. 2011 Apr 29;332(6029):600-3 - PubMed
  123. J Autoimmun. 2010 Nov;35(3):176-80 - PubMed
  124. Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2480-5 - PubMed
  125. Autoimmun Rev. 2014 Apr-May;13(4-5):435-40 - PubMed
  126. Science. 2015 Aug 28;349(6251):993-7 - PubMed
  127. Nat Immunol. 2011 Apr;12(4):304-11 - PubMed
  128. J Autoimmun. 2013 Mar;41:146-51 - PubMed
  129. J Autoimmun. 2005 Aug;25(1):63-71 - PubMed
  130. Gastroenterology. 2012 Jun;142(7):1526-35.e6 - PubMed
  131. J Hepatol. 2014 Nov;61(5):1106-14 - PubMed
  132. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1549-53 - PubMed
  133. Hepatology. 2012 Aug;56(2):677-86 - PubMed
  134. Cell. 2006 Sep 22;126(6):1121-33 - PubMed
  135. Front Immunol. 2018 Jul 19;9:1612 - PubMed

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