CXCR3 blockade combined with cyclosporine A alleviates acute graft-versus-host disease by inhibiting alloreactive donor T cell responses in a murine model

Miao, Shengchao; Tang, Bo; Liu, Huihui; Wang, Zhenhua; Shi, Yongjin; Dong, Yujun; Liu, Wei; Qin, Chenchen; Ren, Hanyun

doi:10.1016/j.molimm.2017.12.010

Cited by 15 publications

(18 citation statements)

References 39 publications

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“…CXCR3 also demonstrates a compelling case. One study showed that CXCR3-expressing Tregs could mitigate aGvHD [211], and more recent studies indicated a positive correlation between CXCR3 expression and aGvHD in mice [210,212,213,214,215,216,217] and humans [200,218]. One of these proposed CXCR3-signaling as a resistance mechanism to CCR5 blockade [200].…”

Section: Resultsmentioning

confidence: 99%

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

Golay

Mlakar

et al. 2019

IJMS

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Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for several malignant and non-malignant diseases at the cost of serious treatment-related toxicities (TRTs). Recent research on extending the benefits of HSCT to more patients and indications has focused on limiting TRTs and improving immunological effects following proper mobilization and engraftment. Increasing numbers of studies report associations between HSCT outcomes and the expression or the manipulation of G protein-coupled receptors (GPCRs). This large family of cell surface receptors is involved in various human diseases. With ever-better knowledge of their crystal structures and signaling dynamics, GPCRs are already the targets for one third of the current therapeutic arsenal. The present paper assesses the current status of animal and human research on GPCRs in the context of selected HSCT outcomes via a systematized survey and analysis of the literature.

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Section: Resultsmentioning

confidence: 99%

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

Golay

Mlakar

et al. 2019

IJMS

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“…In aGVHD model, the activated effector T cells migrate to target tissues and organs to recruit more effector cells, resulting in tissue and organ damage. The role of chemokines in GVHD has been studied by our team and many other researches 11,12 . We found that the increased expression of Cxcl3 was consistent with the enrichment of the pathway.…”

Section: Discussionmentioning

confidence: 99%

“…aGVHD induction in a murine model. The method of induction of aGVHD using radiation-exposed mice and allogeneic bone marrow transplants was described previously 11,12,23 . Brie y, bone marrow cells were acquired from C57BL/6 mice.…”

Section: Methodsmentioning

confidence: 99%

The potential genes mediate the pathogenicity of allogeneic CD4+T cell in aGVHD mouse model

Qin

Cao

et al. 2021

Preprint

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Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). As a transcriptome sequencing technique, ribonucleic acid sequencing (RNA-Seq) is used to study alternative splicing and other forms of alternative isoform expression. Major histocompatibility complex (MHC)-matched and MHC-mismatched mouse bone marrow transplant (BMT) models were built to detect the difference of CD4+ lymphocyte in different tissues based on RNA-seq analysis. Four critical pathways were identified by enrichment analysis, including a lymphoid and a non-lymphoid cell, chemokine receptor binding chemokine, cytokine and cytokine receptor interaction pathway. At the same time, 11 novel hub genes that are most likely to participate in immunoregulatory and enriched pathways were identified, which were further validated by qRT-PCR. Besides, Cxcl7 was verified at the protein level. In summary, we revealed that DEGs and pathways related to immunoregulation played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD.

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“…Some investigations highlighted that the migration of the effector T cells to the target tissues was crucial for the pathogenesis of aGvHD [29,30]. Nowadays, MSCs have been employed as efficient treatment options for aGvHD.…”

Section: Discussionmentioning

confidence: 99%

MiR-223 Derived from Mesenchymal Stem Cell Exosomes Alleviates Acute Graft-Versus-Host Disease

Liu¹,

Zhou²,

Wang³

et al. 2020

Preprint

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Background Mesenchymal stem cells (MSCs) have been utilized in treating acute graft-versus-host disease (aGvHD) as they show strong immunosuppressive capacity, but the mechanisms are not well defined.Methods In this study, we demonstrated that microRNA-223 (miR-223) derived from exosomes secreted by human umbilical cord mesenchymal stem cells (huc-MSCs) and murine compact bone mesenchymal stem cells (mb-MSCs) could inhibit aGvHD progression by reducing the migration and homing of donor T cells in aGvHD mice.Results MiR-223 was one of the conserved microRNAs highly expressed in huc-MSCs exosomes and mMSCs exosomes, which was identified by high-throughput sequencing. MiR-223 derived from MSC exosomes showed enhanced immunosuppressive capacity, as it could inhibit expression of the target gene ICAM-1 and restrain adhesion and migration of T cells in vitro. Moreover, miR-223Agomir was effective in reducing the inflammatory reaction, and declining the donor T cells infiltration into the spleen, liver and intestine in aGvHD mice. Subsequently, it could alleviate aGvHD symptoms. Taken together, the MSC exosome derived miR-223 could attenuate aGvHD in mice through regulating ICAM-1 expression.Conclusions Our results unveil a new role for MSC exosomes derived miR-223 in the treatment of aGvHD.

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CXCR3 blockade combined with cyclosporine A alleviates acute graft-versus-host disease by inhibiting alloreactive donor T cell responses in a murine model

Cited by 15 publications

References 39 publications

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

The potential genes mediate the pathogenicity of allogeneic CD4+T cell in aGVHD mouse model

MiR-223 Derived from Mesenchymal Stem Cell Exosomes Alleviates Acute Graft-Versus-Host Disease

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