Interferon regulatory factor 4 plays a pivotal role in the development of aGVHD-associated colitis.

Autor:	Frueh JT; Department of Pediatrics, Experimental Immunology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany., Campe J; Department of Pediatrics, Experimental Immunology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany., Sunaga-Franze DY; Genomics Platform, Max Delbrueck Center for Molecular Medicine, Berlin Institute of Health, Berlin, Germany., Verheyden NA; Institute for Molecular Medicine, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.; Molecular Immunology, Justus Liebig University Giessen, Giessen, Germany., Ghimire S; Hematology and Oncology Department, Medical Clinic 3, University Hospital Regensburg, Regensburg, Germany., Meedt E; Hematology and Oncology Department, Medical Clinic 3, University Hospital Regensburg, Regensburg, Germany., Haslinger D; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany., Harenkamp S; German Red Cross Blood Service BaWüHe, Frankfurt am Main, Germany., Staudenraus D; Institute for Microbiology, Philipps University, Marburg, Germany., Sauer S; Genomics Platform, Max Delbrueck Center for Molecular Medicine, Berlin Institute of Health, Berlin, Germany., Kreft A; Institute of Pathology, University Medical Center Mainz, Mainz, Germany., Schubert R; Department of Pediatric Medicine, Division of Pneumology, Allergology, Infectious diseaes und Gastroenterology. Frankfurt am Main, Goethe University Frankfurt, Frankfurt, Germany., Lohoff M; Institute for Microbiology, Philipps University, Marburg, Germany., Krueger A; Institute for Molecular Medicine, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.; Molecular Immunology, Justus Liebig University Giessen, Giessen, Germany.; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany., Bonig H; German Red Cross Blood Service BaWüHe, Frankfurt am Main, Germany.; Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt am Main, Germany., Chiocchetti AG; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany., Zeiser R; Department of Internal Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Holler E; Hematology and Oncology Department, Medical Clinic 3, University Hospital Regensburg, Regensburg, Germany., Ullrich E; Department of Pediatrics, Experimental Immunology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.; Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt am Main, Germany.; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, a partnership between DKFZ, University Hospital Frankfurt, Frankfurt, Germany.; University Cancer Center (UCT), Frankfurt am Main, Germany.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2023 Dec 27; Vol. 13 (1), pp. 2296712. Date of Electronic Publication: 2023 Dec 27 (Print Publication: 2024).
DOI:	10.1080/2162402X.2023.2296712
Abstrakt:	Interferon regulatory factor 4 (IRF4) is a master transcription factor that regulates T helper cell (Th) differentiation. It interacts with the Basic leucine zipper transcription factor, ATF-like (BATF), depletion of which in CD4 + T cells abrogates acute graft-versus-host disease (aGVHD)-induced colitis. Here, we investigated the immune-regulatory role of Irf4 in a mouse model of MHC-mismatched bone marrow transplantation. We found that recipients of allogenic Irf4 -/- CD4 + T cells developed less GVHD-related symptoms. Transcriptome analysis of re-isolated donor Irf4 -/- CD4 + T helper (Th) cells, revealed gene expression profiles consistent with loss of effector T helper cell signatures and enrichment of a regulatory T cell (Treg) gene expression signature. In line with these findings, we observed a high expression of the transcription factor BTB and CNC homolog 2; (BACH2) in Irf4 -/- T cells, which is associated with the formation of Treg cells and suppression of Th subset differentiation. We also found an association between BACH2 expression and Treg differentiation in patients with intestinal GVHD. Finally, our results indicate that IRF4 and BACH2 act as counterparts in Th cell polarization and immune homeostasis during GVHD. In conclusion, targeting the BACH2/IRF4-axis could help to develop novel therapeutic approaches against GVHD. Competing Interests: The authors declare no conflict of interest related to this work. E.U. acts as medical advisor of Phialogics and received research funding from Gilead and Bristol-Myers Squibb. R.Z. received honorarium for participation in scientific meetings and advisory boards from Incyte, Mallinckrodt and Novartis. (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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