دورية أكاديمية
أعرض في EDS

Bile acids regulate intestinal antigen presentation and reduce graft-versus-host disease without impairing the graft-versus-leukemia effect.

التفاصيل البيبلوغرافية
العنوان: Bile acids regulate intestinal antigen presentation and reduce graft-versus-host disease without impairing the graft-versus-leukemia effect.
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.
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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
الوصف
تدمد:1592-8721
DOI:10.3324/haematol.2019.242990