scholarly journals Role of Immune Cell Diversity and Heterogeneity in Corneal Graft Survival: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (20) ◽  
pp. 4667
Author(s):  
Jun Zhu ◽  
Takenori Inomata ◽  
Antonio Di Zazzo ◽  
Koji Kitazawa ◽  
Yuichi Okumura ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Allograft Rejection ◽  
Meta Analysis ◽  
Corneal Transplantation ◽  
Solid Organ Transplantation ◽  
Corneal Graft ◽  
Solid Organ ◽  
Innate And Adaptive Immunity ◽  
Corneal Allograft ◽  
Corneal Allograft Rejection

Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.

scholarly journals Effector and Regulatory T Cell Trafficking in Corneal Allograft Rejection

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Afsaneh Amouzegar ◽  
Sunil K. Chauhan
Keyword(s):  
Adhesion Molecules ◽  
Immune Cells ◽  
Allograft Rejection ◽  
Corneal Transplantation ◽  
Lymphoid Tissues ◽  
Cell Trafficking ◽  
Innate And Adaptive Immunity ◽  
Corneal Allograft ◽  
Immune Mediated ◽  
Corneal Allograft Rejection

Corneal transplantation is among the most prevalent and successful forms of solid tissue transplantation in humans. Failure of corneal allograft is mainly due to immune-mediated destruction of the graft, a complex and highly coordinated process that involves elaborate interactions between cells of innate and adaptive immunity. The migration of immune cells to regional lymphoid tissues and to the site of graft plays a central role in the immunopathogenesis of graft rejection. Intricate interactions between adhesion molecules and their counter receptors on immune cells in conjunction with tissue-specific chemokines guide the trafficking of these cells to the draining lymph nodes and ultimately to the site of graft. In this review, we discuss the cascade of chemokines and adhesion molecules that mediate the trafficking of effector and regulatory T cells during corneal allograft rejection.

scholarly journals Leptin Promotes Corneal Allograft Rejection In a Rat Model Via Enhancing Macrophage Activation And Cytokine Production

2021 ◽  
Author(s):  
Jianfeng Yu ◽  
Xiaoqing Chen ◽  
Yingqi Li ◽  
Fen Tang ◽  
Wenru Su ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Corneal Transplantation ◽  
T Helper ◽  
T Helper 1 ◽  
Cervical Lymph Nodes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Corneal Allograft ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Corneal Allograft Rejection

Abstract Obesity is closely related to exacerbated graft rejection and worse graft survival. High leptin levels, caused by excessive adipose cells in obese individuals, may exert a pivotal role in the pathogenesis of allograft rejection. However, the role and underlying mechanism of leptin in allograft rejection remains unclear. This study explored the role and potential mechanism of leptin in allograft rejection in rats. We performed allogeneic corneal transplantation in rats. The recipients were treated with subconjunctival injections of recombinant rat leptin after transplantation. Clinical evaluation, immunohistological assessment, real-time PCR and flow cytometry were administrated. RAW264.7 macrophages were handled with leptin (3 µg/mL) for 4 hours and then were treated with lipopolysaccharide (10ng/mL) for 24 hours. The culture supernatants were acquired for ELISA. NF-κBp65 activation in RAW264.7 macrophages was detected by western blot. Our results showed that the leptin-treated rats had a significantly reduced corneal graft mean survival time. The number of infiltrating F4/80+CD68+ macrophages increased in the leptin-treated corneal grafts. Monocyte chemoattractant protein-1(MCP-1), tumor necrosis factor-α (TNF-α) and interleukin 6(IL-6) mRNA expression level was higher in the leptin-treated corneal grafts than in the control allografts. Leptin treatment notably increased the frequency and number of T helper 1 (Th1) cells and T helper 17 (Th17) cells in rat ipsilateral cervical lymph nodes. Leptin enhanced NF-κBp65 activation and promoted MCP-1, TNF-α and IL-6 production in RAW264.7 macrophages. Leptin promoted corneal allograft rejection by enhancing the recruitment and activation of macrophages.

scholarly journals Resolvin E1 Inhibits Corneal Allograft Rejection in High-Risk Corneal Transplantation

2018 ◽  
Vol 59 (10) ◽  
pp. 3911 ◽  
Author(s):  
Han Wang ◽  
Qingqing Zhao ◽  
Dan Luo ◽  
Yizhou Yin ◽  
Ting Li ◽  
...  
Keyword(s):  
High Risk ◽  
Allograft Rejection ◽  
Corneal Transplantation ◽  
Corneal Allograft ◽  
Corneal Allograft Rejection

scholarly journals MicroRNA-122 ameliorates corneal allograft rejection through the downregulation of its target CPEB1

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Ting Wang ◽  
Fengjie Li ◽  
Wenwen Geng ◽  
Qingguo Ruan ◽  
Weiyun Shi
Keyword(s):  
Allograft Rejection ◽  
Transplant Rejection ◽  
Corneal Transplantation ◽  
Human Organ ◽  
Corneal Allograft ◽  
Corneal Graft Rejection ◽  
Transplantation Rejection ◽  
Element Binding Protein ◽  
Induced Apoptosis ◽  
Corneal Allograft Rejection

Abstract Transplant rejection is a major cause of corneal transplantation failure. MicroRNAs (miRNAs) are a family of small RNAs that regulates gene expression in a sequence-specific manner. miRNAs have recently been shown to have important roles in human organ transplantation, but reports of miRNAs directly associated with corneal transplantation rejection remain limited. To investigate the role of miRNAs during corneal allograft rejection, we established a mouse penetrating keratoplasty model and used microarrays to screen for differentially expressed miRNAs. Our results revealed that the expression of miR-122 was significantly decreased in the allogeneic group. Consistent with this result, the expression of cytoplasmic polyadenylation element-binding protein-1 (CPEB1), a direct target of miR-122, was significantly increased. Further analysis demonstrated that miR-122 inhibited inflammatory cytokine-induced apoptosis in corneal keratocytes through the downregulation of its target CPEB1. We also found that increased miR-122 expression significantly reduced the risk of corneal transplantation rejection. Thus, our results indicate that miR-122 is an important miRNA associated with corneal graft rejection and can be used as a therapeutic target for the prevention of immune rejection after keratoplasty.

scholarly journals The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in Allogeneic Corneal Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Shang Li ◽  
Jing Yu ◽  
Chungang Guo ◽  
Ying Jie ◽  
Zhiqiang Pan
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Aqueous Humor ◽  
Allograft Rejection ◽  
Corneal Transplantation ◽  
Allograft Survival ◽  
Survival Group ◽  
Corneal Allograft ◽  
Group 3 ◽  
Corneal Allograft Rejection

Purpose. CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods. A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry. The related cytokines in aqueous humor were also analyzed. Results. The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group were significantly higher than those in the rejection group. And the expression trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN-γ, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly increased in the rejection group at the 3rd week after corneal transplantation. Conclusion. LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.

scholarly journals Advanced Genomics-Based Approaches for Defining Allograft Rejection With Single Cell Resolution

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiffany Shi ◽  
Krishna Roskin ◽  
Brian M. Baker ◽  
E. Steve Woodle ◽  
David Hildeman
Keyword(s):  
Single Cell ◽  
Allograft Rejection ◽  
Immune Cell ◽  
Transplant Rejection ◽  
Solid Organ Transplantation ◽  
Genomic Analysis ◽  
Solid Organ ◽  
Single Cell Level ◽  
Cell Level ◽  
Network Analyses

Solid organ transplant recipients require long-term immunosuppression for prevention of rejection. Calcineurin inhibitor (CNI)-based immunosuppressive regimens have remained the primary means for immunosuppression for four decades now, yet little is known about their effects on graft resident and infiltrating immune cell populations. Similarly, the understanding of rejection biology under specific types of immunosuppression remains to be defined. Furthermore, development of innovative, rationally designed targeted therapeutics for mitigating or preventing rejection requires a fundamental understanding of the immunobiology that underlies the rejection process. The established use of microarray technologies in transplantation has provided great insight into gene transcripts associated with allograft rejection but does not characterize rejection on a single cell level. Therefore, the development of novel genomics tools, such as single cell sequencing techniques, combined with powerful bioinformatics approaches, has enabled characterization of immune processes at the single cell level. This can provide profound insights into the rejection process, including identification of resident and infiltrating cell transcriptomes, cell-cell interactions, and T cell receptor α/β repertoires. In this review, we discuss genomic analysis techniques, including microarray, bulk RNAseq (bulkSeq), single-cell RNAseq (scRNAseq), and spatial transcriptomic (ST) techniques, including considerations of their benefits and limitations. Further, other techniques, such as chromatin analysis via assay for transposase-accessible chromatin sequencing (ATACseq), bioinformatic regulatory network analyses, and protein-based approaches are also examined. Application of these tools will play a crucial role in redefining transplant rejection with single cell resolution and likely aid in the development of future immunomodulatory therapies in solid organ transplantation.

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