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Trends in Molecular Research for Transplantation Immunology
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Trends in Molecular Research for Transplantation Immunology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (20 March 2020) | Viewed by 25250

Special Issue Editor

Prof. Dr. Carla C. Baan

E-Mail Website1 Website2
Guest Editor
Department of Internal Medicine, Section of Transplantation and Nephrology, Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Interests: organ transplantation; transplantation immunology; immunosuppressants; T cells; B cells; CD4; CD8

Special Issue Information

Dear Colleagues,

This Special Issue of IJMS brings articles in all areas related to transplantation immunology including tissue injury, transplant rejection and acceptance, and immunosuppression to highlight both progress and gaps in knowledge. It covers our current understanding of antigen recognition, signal transduction, epigenetics, cell signaling, and the regulatory and effector mechanisms of the innate and adaptive immune systems. This also includes the new frontiers in molecular diagnostics for antibody and T cell-mediated cellular rejection in patients after solid organ transplantation. Such information has proven important in understanding the action of immunosuppressive drugs and will prove useful in the design of new immunotherapies. This Issue offers a range of articles across the fields of clinical and experimental transplantation.

Specific Topics covered in this Issue include (but not limited to) the following: genome editing, ischemia reperfusion injury, tissue repair, cell therapy, innate immune systems in allorecognition, adaptive immunity, immune regulation, HLA and antibodies, pathology, new technical developments, the future of immunosuppression.

Prof. Dr. Carla C. Baan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Transplantation immunology
  • Immunosuppression
  • Antigen recognition
  • Innate and adaptive immune system
  • Cellular rejection
  • Immunosuppressive drugs
  • Immunotherapy
  • Immune regulation
  • T cells
  • B cells
  • CD4
  • CD8

Published Papers (6 papers)

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Research

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16 pages, 4104 KiB  
Article
IL-27Rα: A Novel Molecular Imaging Marker for Allograft Rejection
by Shanshan Zhao, Dai Shi, Chen Su, Wen Jiang, Chao Zhang, Ting Liang and Guihua Hou
Int. J. Mol. Sci. 2020, 21(4), 1315; https://doi.org/10.3390/ijms21041315 - 15 Feb 2020
Cited by 4 | Viewed by 2237
Abstract
Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27Rα was up-regulated in alloreactive CD4+ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27Rα could be used [...] Read more.
Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27Rα was up-regulated in alloreactive CD4+ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27Rα could be used in monitoring allogeneic graft rejection both in vitro and in vivo. Allogeneic (C57BL/6 donor to BALB/c recipient) and syngeneic (BALB/c both as donor and recipient) skin grafted mouse models were established. The expression of IL-27Rα in grafts was detected. The radio-probe, 125I-anti-IL-27Rα mAb, was prepared. Dynamic whole-body phosphor-autoradiography, ex vivo biodistribution and immunofluorescence staining were performed. The results showed that the highest expression of IL-27Rα was detected in allogeneic grafts on day 10 post transplantation (top period of allorejection). 125I-anti-IL-27Rα mAb was successfully prepared with higher specificity and affinity. Whole-body phosphor-autoradiography showed higher radioactivity accumulation in allogeneic grafts than syngeneic grafts on day 10. The uptake of 125I-anti-IL-27Rα mAb in allogeneic grafts could be almost totally blocked by pre-injection with excess unlabeled anti-IL-27Rα mAb. Interestingly, we found that 125I-anti-IL-27Rα mAb accumulated in allogeneic grafts, along with weaker inflammation earlier on day 6. The high uptake of 125I-anti-IL-27Rα mAb was correlated with the higher infiltrated IL-27Rα positive cells (CD3+/CD68+) in allogeneic grafts. In conclusion, IL-27Rα may be a novel molecular imaging marker to predict allorejection. Full article
(This article belongs to the Special Issue Trends in Molecular Research for Transplantation Immunology)
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13 pages, 2400 KiB  
Article
Immunomonitoring of Tacrolimus in Healthy Volunteers: The First Step from PK- to PD-Based Therapeutic Drug Monitoring?
by Aliede E. in ‘t Veld, Hendrika W. Grievink, Mahdi Saghari, Frederik E. Stuurman, Marieke L. de Kam, Aiko P. J. de Vries, Brenda C. M. de Winter, Jacobus Burggraaf, Adam F. Cohen and Matthijs Moerland
Int. J. Mol. Sci. 2019, 20(19), 4710; https://doi.org/10.3390/ijms20194710 - 23 Sep 2019
Cited by 12 | Viewed by 5773
Abstract
Therapeutic drug monitoring is routinely performed to maintain optimal tacrolimus concentrations in kidney transplant recipients. Nonetheless, toxicity and rejection still occur within an acceptable concentration-range. To have a better understanding of the relationship between tacrolimus dose, tacrolimus concentration, and its effect on the [...] Read more.
Therapeutic drug monitoring is routinely performed to maintain optimal tacrolimus concentrations in kidney transplant recipients. Nonetheless, toxicity and rejection still occur within an acceptable concentration-range. To have a better understanding of the relationship between tacrolimus dose, tacrolimus concentration, and its effect on the target cell, we developed functional immune tests for the quantification of the tacrolimus effect. Twelve healthy volunteers received a single dose of tacrolimus, after which intracellular and whole blood tacrolimus concentrations were measured and were related to T cell functionality. A significant correlation was found between tacrolimus concentrations in T cells and whole blood concentrations (r = 0.71, p = 0.009), while no correlation was found between tacrolimus concentrations in peripheral blood mononuclear cells (PBMCs) and whole blood (r = 0.35, p = 0.27). Phytohemagglutinin (PHA) induced the production of IL-2 and IFNγ, as well as the inhibition of CD71 and CD154 expression on T cells at 1.5 h post-dose, when maximum tacrolimus levels were observed. Moreover, the in vitro tacrolimus effect of the mentioned markers corresponded with the ex vivo effect after dosing. In conclusion, our results showed that intracellular tacrolimus concentrations mimic whole blood concentrations, and that PHA-induced cytokine production (IL-2 and IFNγ) and activation marker expression (CD71 and CD154) are suitable readout measures to measure the immunosuppressive effect of tacrolimus on the T cell. Full article
(This article belongs to the Special Issue Trends in Molecular Research for Transplantation Immunology)
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12 pages, 1456 KiB  
Article
Early Immunological Effects of Ischemia-Reperfusion Injury: No Modulation by Ischemic Preconditioning in a Randomised Crossover Trial in Healthy Humans
by Thomas H. Lange, Marco Eijken, Carla Baan, Mikkel Steen Petersen, Bo Martin Bibby, Bente Jespersen and Bjarne K. Møller
Int. J. Mol. Sci. 2019, 20(12), 2877; https://doi.org/10.3390/ijms20122877 - 13 Jun 2019
Cited by 5 | Viewed by 2701
Abstract
Ischemic preconditioning (IPC) has been protective against ischemia-reperfusion injury (IRI), but the underlying mechanism is poorly understood. We examined whether IPC modulates the early inflammatory response after IRI. Nineteen healthy males participated in a randomised crossover trial with and without IPC before IRI. [...] Read more.
Ischemic preconditioning (IPC) has been protective against ischemia-reperfusion injury (IRI), but the underlying mechanism is poorly understood. We examined whether IPC modulates the early inflammatory response after IRI. Nineteen healthy males participated in a randomised crossover trial with and without IPC before IRI. IPC and IRI were performed by cuff inflation on the forearm. IPC consisted of four cycles of five minutes followed by five minutes of reperfusion. IRI consisted of twenty minutes followed by 15 min of reperfusion. Blood was collected at baseline, 0 min, 85 min and 24 h after IRI. Circulating monocytes, T-cells subsets and dendritic cells together with intracellular activation markers were quantified by flow cytometry. Luminex measured a panel of inflammation-related cytokines in plasma. IRI resulted in dynamic regulations of the measured immune cells and their intracellular activation markers, however IPC did not significantly alter these patterns. Neither IRI nor the IPC protocol significantly affected the levels of inflammatory-related cytokines. In healthy volunteers, it was not possible to detect an effect of the investigated IPC-protocol on early IRI-induced inflammatory responses. This study indicates that protective effects of IPC on IRI is not explained by direct modulation of early inflammatory events. Full article
(This article belongs to the Special Issue Trends in Molecular Research for Transplantation Immunology)
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16 pages, 3395 KiB  
Article
Cannabinoids Reduce Inflammation but Inhibit Lymphocyte Recovery in Murine Models of Bone Marrow Transplantation
by Iman Khuja, Zhanna Yekhtin, Reuven Or and Osnat Almogi-Hazan
Int. J. Mol. Sci. 2019, 20(3), 668; https://doi.org/10.3390/ijms20030668 - 4 Feb 2019
Cited by 28 | Viewed by 7130
Abstract
Cannabinoids, the biologically active constituents of Cannabis, have potent neuronal and immunological effects. However, the basic and medical research dedicated to medical cannabis and cannabinoids is limited. The influence of these treatments on hematologic reconstitution and on the development of graft versus host [...] Read more.
Cannabinoids, the biologically active constituents of Cannabis, have potent neuronal and immunological effects. However, the basic and medical research dedicated to medical cannabis and cannabinoids is limited. The influence of these treatments on hematologic reconstitution and on the development of graft versus host disease (GVHD) after bone marrow transplantation (BMT) is largely unknown. In this research, we compared the influence of D9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on lymphocyte activation in vitro and in murine BMT models. Our in vitro results demonstrate that these treatments decrease activated lymphocyte proliferation and affect cytokine secretion. We also discovered that CBD and THC utilize different receptors to mediate these effects. In vivo, in a syngeneic transplantation model, we demonstrate that all treatments inhibit lymphocyte reconstitution and show the inhibitory role of the cannabinoid receptor type 2 (CB2) on lymphocyte recovery. Although pure cannabinoids exhibited a superior effect in vitro, in an allogeneic (C57BL/6 to BALB/c) BMT mouse model, THC-high and CBD-high cannabis extracts treatment reduced the severity of GVHD and improved survival significantly better than the pure cannabinoids. Our results highlights the complexity of using cannabinoids-based treatments and the need for additional comparative scientific results. Full article
(This article belongs to the Special Issue Trends in Molecular Research for Transplantation Immunology)
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Review

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21 pages, 1905 KiB  
Review
The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens
by Jose-Ignacio Rodriguez-Barbosa, Pascal Schneider, Luis Graca, Leo Bühler, Jose-Antonio Perez-Simon and Maria-Luisa del Rio
Int. J. Mol. Sci. 2020, 21(9), 3347; https://doi.org/10.3390/ijms21093347 - 9 May 2020
Cited by 8 | Viewed by 4004
Abstract
Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor [...] Read more.
Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR. Full article
(This article belongs to the Special Issue Trends in Molecular Research for Transplantation Immunology)
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14 pages, 252 KiB  
Review
Reparative and Regenerative Effects of Mesenchymal Stromal Cells—Promising Potential for Kidney Transplantation?
by Merel Pool, Henri Leuvenink and Cyril Moers
Int. J. Mol. Sci. 2019, 20(18), 4614; https://doi.org/10.3390/ijms20184614 - 18 Sep 2019
Cited by 10 | Viewed by 2433
Abstract
Mesenchymal stromal cells (MSCs) possess reparative, regenerative and immunomodulatory properties. The current literature suggests that MSCs could improve kidney transplant outcome via immunomodulation. In many clinical domains, research has also focussed on the regenerative and reparative effects of therapies with MSCs. However, in [...] Read more.
Mesenchymal stromal cells (MSCs) possess reparative, regenerative and immunomodulatory properties. The current literature suggests that MSCs could improve kidney transplant outcome via immunomodulation. In many clinical domains, research has also focussed on the regenerative and reparative effects of therapies with MSCs. However, in the field of transplantation, data on this subject remain scarce. This review provides an overview of what is known about the regenerative and reparative effects of MSCs in various fields ranging from wound care to fracture healing and also examines the potential of these promising MSC properties to improve the outcome of kidney transplantations. Full article
(This article belongs to the Special Issue Trends in Molecular Research for Transplantation Immunology)
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