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CLINICAL TRIAL article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1529176
This article is part of the Research Topic Localized Immunomodulation Approaches for Transplantation Tolerance View all articles
Preventive Hyperbaric Oxygen Therapy Improves Acute Graft-Versus-Host Disease by Activating the Nrf2/HO-1 Pathway
Provisionally accepted
Chao Xue 1,2
Hao Chen 2* Yiou Zhao 3* Dai Yuan 2*
Xiaosheng Fang 2 Mei Ding 2* Huiting Qu 2* Xin Wang 2* Xueling Ge 2* Kang Lu 2*
Yujie Jiang 2*- 1 First Hospital, Peking University, Beijing, China
- 2 Shandong Provincial Hospital, Jinan, Shandong Province, China
- 3 Changchun University of Science and Technology, Changchun, Jilin Province, China
Background: Hyperbaric oxygen therapy (HBOT) has been confirmed as an effective and economical therapeutic modality for treating hemorrhagic cystitis (HC), whether induced by infection or acute graft-versus-host disease (aGVHD), in transplant recipients. However, little is known about the potential benefits of HBOT in treating aGVHD. In the present study, the effect of HBOT on aGVHD and its underlying mechanisms were explored.Methods: The beneficial effects of HBOT on aGVHD were investigated in a murine model. The manifestations, pathological alterations, reactive oxygen species (ROS) of target organs, and survival data of the recipient mice were collected. Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and downstream heme-oxygenase 1 (HO-1) expression in mouse samples were determined by western blot and immunohistochemistry analyses. ML385, an inhibitor of Nrf2, was used to validate the protective role of Nrf2 in the beneficial effect of HBO on aGVHD. Furthermore, we initiated a clinical cohort study and collected data from the patients with definite aGVHD before and after HBOT to validate the preclinical conclusions.Results: We found that aGVHD can be alleviated by HBOT in mice, which was associated with a significantly prolonged overall survival (OS) and improved pathological injury, whereas inhibition of Nrf2 had the opposite effect. HBOT decreased the levels of ROS and proinflammatory cytokines, including IL-6 and TNF-α, but upregulated the expression levels of Nrf2 and its downstream antioxidant enzymes HO-1. In the clinical cohort study, the incidence of grade I-III aGVHD in the combination arm containing HBOT was significantly lower than that in the HBOT-free cohort.Conclusion: Preventive HBOT can improve aGVHD by activating the Nrf2/HO-1 signal transduction pathway, and HBOT may represent a potentially feasible approach for aGVHD prevention and treatment.
Keywords: allogeneic hematopoietic stem cell transplantation, Acute graft-versushost disease, hyperbaric oxygen therapy, Erythroid-derived 2-related factor 2 (Nrf2), Reactive Oxygen Species
Received: 16 Nov 2024; Accepted: 10 Feb 2025.
Copyright: © 2025 Xue, Chen, Zhao, Yuan, Fang, Ding, Qu, Wang, Ge, Lu and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hao Chen, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
Yiou Zhao, Changchun University of Science and Technology, Changchun, 130022, Jilin Province, China
Dai Yuan, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
Mei Ding, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
Huiting Qu, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
Xin Wang, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
Xueling Ge, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
Kang Lu, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
Yujie Jiang, Shandong Provincial Hospital, Jinan, 250021, Shandong Province, China
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