High expression of heme oxygenase-1 in target organs may attenuate acute graft-versus-host disease through regulation of immune balance of TH17/Treg

Yu, Meisheng; Wang, Jishi; Fang, Qin; Liu, Ping; Chen, Shuya; Zhe, Nana; Lin, Xiaojing; Zhang, Yaming; Zhao, Jiangyuan; Zhou, Zhen

doi:10.1016/j.trim.2016.05.002

Cited by 20 publications

(15 citation statements)

References 42 publications

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“…It has been proposed that a higher HO-1 expression level prevents the progression of GVHD and acts prophylactically on sinusoid obstruction syndrome (SOS), while promoting relapse [39][40][41]. Although the results of this study suggest that the higher expression of HO-1 is associated with favorable survival outcomes after allo-HSCT, the higher expression of HO-1 has not been shown to affect the risk of disease relapse or the development of GVHD.…”

Section: Discussioncontrasting

confidence: 57%

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Horio

Morishita

Mizuno

et al. 2020

Cancers

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Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.

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Section: Discussioncontrasting

confidence: 57%

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Horio

Morishita

Mizuno

et al. 2020

Cancers

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“…Given that both the amount and the function of Tregs were inhibited in vitiligo, we speculated that restoring Treg function may also be effective in treating vitiligo. Previous studies have concluded that HO‐1 expression is necessary for Tregs to exert their immunoregulatory function . Up‐regulation of HO‐1 activity in vivo can inhibit several immune response, including the proliferation of lymphocytes and cytotoxic immune cells‐mediated cytotoxicity .…”

Section: Discussionmentioning

confidence: 99%

HO‐1 regulates the function of Treg: Association with the immune intolerance in vitiligo

Zhang

Cui

Chang

et al. 2018

J Cellular Molecular Medi

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In vitiligo, cutaneous depigmentation is accompanied by increased T cell cytolytic activity targeting melanocytes, indicating that autoimmune tolerance is disrupted. The inhibited amount and function of Tregs have been indicated to be involved in the autoimmune intolerance in vitiligo, however, with the conclusion still controversial and the involved mechanism unknown. In this study, we explored the molecular and cellular alterations accounting for the impaired Treg response in vitiligo. Our results showed that the amount of Tregs was drastically reduced in peripheral blood of active vitiligo patients. Furthermore, the immunoregulatory function of Tregs was attenuated, with lower expression of CTLA4, IL‐10 and TGF‐β. Moreover, the expression of HO‐1, a functional modulator of Tregs, was decreased in vitiligo Tregs, and the concentrations of HO‐1 metabolites, including bilirubin, CoHb and iron, were correspondingly decreased in serum of vitiligo patients. In addition, we treated the Tregs from vitiligo patients with Hemin, an agonist of HO‐1, and found that enhanced HO‐1 expression restored the function of Tregs by up‐regulating IL‐10 expression. Our study demonstrates the essential role of HO‐1 in the impaired Treg response in vitiligo and indicates the potential of HO‐1 as a therapeutic target in vitiligo management.

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“…GvHD is commonly observed after hematopoietic stem cell transplants, when T cells present in the graft attack the tissues of the transplanted recipient. After perceiving host tissue antigens, among them the human leukocyte antigens, as antigenically foreign, T cells produce an excess of cytokines, including tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) ( 25 , 27 , 71 ).…”

Section: Innate Immunity As a Potential Trigger Of Gvhdmentioning

confidence: 99%

“…On the other hand, chronic activation of the MBL pathway is most likely an important element in BM aging and myelodysplasia ( 20 – 23 ). This pathway also likely contributes based on some clinical observations to induction of graft-versus-host disease (GvHD) after histoincompatible hematopoietic transplantation ( 24 – 27 ).…”

Section: Introductionmentioning

confidence: 99%

The Emerging Link Between the Complement Cascade and Purinergic Signaling in Stress Hematopoiesis

et al. 2018

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Innate immunity plays an important role in orchestrating the immune response, and the complement cascade (ComC) is a major component of this ancient defense system, which is activated by the classical-, alternative-, or mannan-binding lectin (MBL) pathways. However, the MBL-dependent ComC-activation pathway has been somewhat underappreciated for many years; recent evidence indicates that it plays a crucial role in regulating the trafficking of hematopoietic stem/progenitor cells (HSPCs) by promoting their egress from bone marrow (BM) into peripheral blood (PB). This process is initiated by the release of danger-associated molecular patterns (DAMPs) from BM cells, including the most abundant member of this family, adenosine triphosphate (ATP). This nucleotide is well known as a ubiquitous intracellular molecular energy source, but when secreted becomes an important extracellular nucleotide signaling molecule and mediator of purinergic signaling. What is important for the topic of this review, ATP released from BM cells is recognized as a DAMP by MBL, and the MBL-dependent pathway of ComC activation induces a state of “sterile inflammation” in the BM microenvironment. This activation of the ComC by MBL leads to the release of several potent mediators, including the anaphylatoxins C5a and desArgC5a, which are crucial for egress of HSPCs into the circulation. In parallel, as a ligand for purinergic receptors, ATP affects mobilization of HSPCs by activating other pro-mobilizing pathways. This emerging link between the release of ATP, which on the one hand is an activator of the MBL pathway of the ComC and on the other hand is a purinergic signaling molecule, will be discussed in this review. This mechanism plays an important role in triggering defense mechanisms in response to tissue/organ injury but may also have a negative impact by triggering autoimmune disorders, aging of HSPCs, induction of myelodysplasia, and graft-versus-host disease after transplantation of histoincompatible hematopoietic cells.

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High expression of heme oxygenase-1 in target organs may attenuate acute graft-versus-host disease through regulation of immune balance of TH17/Treg

Cited by 20 publications

References 42 publications

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

HO‐1 regulates the function of Treg: Association with the immune intolerance in vitiligo

The Emerging Link Between the Complement Cascade and Purinergic Signaling in Stress Hematopoiesis

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