دورية أكاديمية
Bile acids regulate intestinal antigen presentation and reduce graft-versus-host disease without impairing the graft-versus-leukemia effect.
العنوان: | Bile acids regulate intestinal antigen presentation and reduce graft-versus-host disease without impairing the graft-versus-leukemia effect. |
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المؤلفون: | Haring E; Department of Medicine I, Medical Center - University of Freiburg, Germany., Uhl FM; Department of Medicine I, Medical Center - University of Freiburg, Germany., Andrieux G; Institute of Medical Bioinformatics and Systems Medicine, University of Freiburg, Freiburg, Germany., Proietti M; Institute for Immunodeficiency, CCI, Medical Center, University of Freiburg, Freiburg, Germany., Bulashevska A; Institute for Immunodeficiency, CCI, Medical Center, University of Freiburg, Freiburg, Germany., Sauer B; Department of Medicine I, Medical Center - University of Freiburg, Germany., Braun LM; Department of Medicine I, Medical Center - University of Freiburg, Germany., de Vega Gomez E; Department of Medicine I, Medical Center - University of Freiburg, Germany., Esser PR; Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Martin SF; Department of Dermatology, Medical Center - University of Freiburg, Freiburg, Germany., Pfeifer D; Department of Medicine I, Medical Center - University of Freiburg, Germany., Follo M; Department of Medicine I, Medical Center - University of Freiburg, Germany., Schmitt-Graeff A; University of Freiburg, Germany., Buescher J; Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Duyster J; Department of Medicine I, Medical Center - University of Freiburg, Germany., Grimbacher B; Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Boerries M; Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Pearce EL; Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Zeiser R; Department of Medicine I, Medical Center - University of Freiburg, Germany., Apostolova P; Department of Medicine I, Medical Center - University of Freiburg, Germany. |
المصدر: | Haematologica [Haematologica] 2021 Aug 01; Vol. 106 (8), pp. 2131-2146. Date of Electronic Publication: 2021 Aug 01. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Ferrata Storti Foundation Country of Publication: Italy NLM ID: 0417435 Publication Model: Electronic Cited Medium: Internet ISSN: 1592-8721 (Electronic) Linking ISSN: 03906078 NLM ISO Abbreviation: Haematologica Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1999- : Pavia, Italy : Ferrata Storti Foundation Original Publication: Pavia [etc.] |
مواضيع طبية MeSH: | Graft vs Host Disease*/prevention & control , Hematopoietic Stem Cell Transplantation*/adverse effects , Leukemia*, Animals ; Antigen Presentation ; Bile Acids and Salts ; Humans ; Intestines ; Mice ; Transplantation, Homologous |
مستخلص: | Acute graft-versus-host disease causes significant mortality in patients undergoing allogeneic hematopoietic cell transplantation. Immunosuppressive treatment for graft-versus-host disease can impair the beneficial graft-versus-leukemia effect and facilitate malignancy relapse. Therefore, novel approaches that protect and regenerate injured tissues without impeding the donor immune system are needed. Bile acids regulate multiple cellular processes and are in close contact with the intestinal epithelium, a major target of acute graft-versus-host disease. Here, we found that the bile acid pool is reduced following graft-versus-host disease induction in a preclinical model. We evaluated the efficacy of bile acids to protect the intestinal epithelium without reducing anti-tumor immunity. We observed that application of bile acids decreased cytokine-induced cell death in intestinal organoids and cell lines. Systemic prophylactic administration of tauroursodeoxycholic acid, the most potent compound in our in vitro studies, reduced graft-versus-host disease severity in three different murine transplantation models. This effect was mediated by decreased activity of the antigen presentation machinery and subsequent prevention of apoptosis of the intestinal epithelium. Moreover, bile acid administration did not alter the bacterial composition in the intestine suggesting that its effects are cell-specific and independent of the microbiome. Treatment of human and murine leukemic cell lines with tauroursodeoxycholic acid did not interfere with the expression of antigen presentation-related molecules. Systemic T cell expansion and especially their cytotoxic capacity against leukemic cells remained intact. This study establishes a role for bile acids in the prevention of acute graft-versus-host disease without impairing the graft-versus-leukemia effect. In particular, we provide a scientific rationale for the systematic use of tauroursodeoxycholic acid in patients undergoing allogeneic hematopoietic cell transplantation. |
References: | Annu Rev Biochem. 2003;72:137-74. (PMID: 12543708) Biol Blood Marrow Transplant. 2014 Jan;20(1):4-13. (PMID: 24018392) Hepatology. 2001 Nov;34(5):964-71. (PMID: 11679967) J Immunol. 2009 Nov 15;183(10):6251-61. (PMID: 19864602) Biol Blood Marrow Transplant. 2004 Sep;10(9):635-44. (PMID: 15319775) J Clin Invest. 1999 Jan;103(1):137-45. (PMID: 9884343) JCI Insight. 2018 Sep 20;3(18):. (PMID: 30232288) Blood. 2019 Mar 21;133(12):1290-1297. (PMID: 30578254) Blood. 2016 Mar 24;127(12):1544-50. (PMID: 26729898) Dig Liver Dis. 2014 Apr;46(4):302-12. (PMID: 24411485) Cell Death Differ. 1999 Sep;6(9):842-54. (PMID: 10510466) J Hepatol. 1998 Jan;28(1):99-106. (PMID: 9537871) Biol Blood Marrow Transplant. 2014 Jan;20(1):135-8. (PMID: 24141008) Biol Blood Marrow Transplant. 2007 Feb;13(2):206-17. (PMID: 17241926) J Clin Invest. 1998 Jun 15;101(12):2790-9. (PMID: 9637713) N Engl J Med. 2017 Nov 30;377(22):2167-2179. (PMID: 29171820) Transplantation. 2001 Dec 15;72(11):1803-7. (PMID: 11740392) Sci Immunol. 2019 Dec 6;4(42):. (PMID: 31811055) Angiology. 2015 Nov;66(10):941-9. (PMID: 25818106) Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4523-30. (PMID: 20837534) J Lipid Res. 2009 Sep;50(9):1721-34. (PMID: 19417220) Mol Med. 1998 Mar;4(3):165-78. (PMID: 9562975) J Lipid Res. 2006 Feb;47(2):241-59. (PMID: 16299351) Blood. 2017 Feb 23;129(8):927-933. (PMID: 27940475) Blood. 2012 Jul 5;120(1):223-31. (PMID: 22535662) Gut Liver. 2015 May 23;9(3):332-9. (PMID: 25918262) Mol Endocrinol. 2010 Jun;24(6):1151-64. (PMID: 20371703) Br J Haematol. 2012 May;157(3):403-7. (PMID: 22225419) Curr Opin Gastroenterol. 2014 May;30(3):332-8. (PMID: 24625896) Biochem Biophys Res Commun. 2002 Nov 15;298(5):714-9. (PMID: 12419312) Oncotarget. 2015 Sep 29;6(29):28011-25. (PMID: 26293671) J Immunol. 2017 Jul 15;199(2):718-733. (PMID: 28607110) Hepatology. 2001 Mar;33(3):616-26. (PMID: 11230742) J Nutr. 2004 Feb;134(2):483-6. (PMID: 14747693) J Pharmacol Exp Ther. 2004 Nov;311(2):845-52. (PMID: 15190125) Gut. 2011 Apr;60(4):463-72. (PMID: 21242261) J Exp Med. 2012 May 7;209(5):903-11. (PMID: 22547653) Nat Commun. 2019 Dec 13;10(1):5695. (PMID: 31836702) Bone Marrow Transplant. 1992 Oct;10(4):367-72. (PMID: 1422493) J Exp Med. 2011 Feb 14;208(2):285-94. (PMID: 21282378) BMC Biochem. 2001;2:11. (PMID: 11707155) Hepatology. 2004 Jun;39(6):1563-73. (PMID: 15185297) Biol Blood Marrow Transplant. 2014 May;20(5):640-5. (PMID: 24492144) J Hepatol. 2015 Apr;62(4):871-8. (PMID: 25463533) J Biol Chem. 2000 Jun 30;275(26):20210-6. (PMID: 10770953) Methods Mol Biol. 2013;945:319-28. (PMID: 23097115) J Gastroenterol. 2015 Jul;50(7):707-19. (PMID: 25708288) Curr Issues Mol Biol. 2007 Jul;9(2):123-38. (PMID: 17489439) Immunity. 2019 Nov 19;51(5):885-898.e7. (PMID: 31542340) World J Gastroenterol. 2009 Feb 21;15(7):804-16. (PMID: 19230041) |
المشرفين على المادة: | 0 (Bile Acids and Salts) |
تواريخ الأحداث: | Date Created: 20200718 Date Completed: 20210928 Latest Revision: 20210928 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8327708 |
DOI: | 10.3324/haematol.2019.242990 |
PMID: | 32675222 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1592-8721 |
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DOI: | 10.3324/haematol.2019.242990 |