Frueh, Jochen T. and Campe, Julia and Sunaga-Franze, Daniele Yumi and Verheyden, Nikita A. and Ghimire, Sakhila and Meedt, Elisabeth and Haslinger, Denise and Harenkamp, Sabine and Staudenraus, Daniel and Sauer, Sascha and Kreft, Andreas and Schubert, Ralf and Lohoff, Michael and Krueger, Andreas and Bonig, Halvard and Chiocchetti, Andreas G. and Zeiser, Robert and Holler, Ernst and Ullrich, Evelyn (2024) Interferon regulatory factor 4 plays a pivotal role in the development of aGVHD-associated colitis. ONCOIMMUNOLOGY, 13 (1): 2296712. ISSN 2162-402X,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; T-CELLS; RETROSPECTIVE ANALYSIS; TRANSCRIPTION; IRF4; GVHD; TH1; DIFFERENTIATION; SURVIVAL; MICE; Acute GVHD; BACH2; IRF4; T helper cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Aug 2025 10:00 |
| Last Modified: | 20 Aug 2025 10:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65508 |
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