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  1. Article ; Online: The T-cell environment: may the regulatory force be with you.

    Luo, Xunrong / Knechtle, Stuart

    Kidney international

    2023  Volume 105, Issue 1, Page(s) 20–22

    Abstract: In the study by Sasaki et al. in this issue, the authors studied infusions of ex vivo-expanded regulatory T cells in a highly clinically relevant nonhuman primate kidney transplant model. This commentary will aim to discuss the use of regulatory T cells ... ...

    Abstract In the study by Sasaki et al. in this issue, the authors studied infusions of ex vivo-expanded regulatory T cells in a highly clinically relevant nonhuman primate kidney transplant model. This commentary will aim to discuss the use of regulatory T cells in the wider context of transplantation, with particular emphasis on the milieu and various engineering potentials to enhance their function, as well as their relationship to other cell populations with regulatory capacity.
    MeSH term(s) Animals ; T-Lymphocytes, Regulatory ; Kidney Transplantation/adverse effects
    Language English
    Publishing date 2023-11-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2023.10.023
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  2. Article ; Online: Novel Approaches to Immunomodulation for Solid Organ Transplantation.

    Husain, Irma / Luo, Xunrong

    Annual review of medicine

    2023  Volume 75, Page(s) 369–380

    Abstract: Despite significant advances in the field of transplantation in the past two decades, current clinically available therapeutic options for immunomodulation remain fairly limited. The advent of calcineurin inhibitor-based immunosuppression has led to ... ...

    Abstract Despite significant advances in the field of transplantation in the past two decades, current clinically available therapeutic options for immunomodulation remain fairly limited. The advent of calcineurin inhibitor-based immunosuppression has led to significant success in improving short-term graft survival; however, improvements in long-term graft survival have stalled. Solid organ transplantation provides a unique opportunity for immunomodulation of both the donor organ prior to implantation and the recipient post transplantation. Furthermore, therapies beyond targeting the adaptive immune system have the potential to ameliorate ischemic injury to the allograft and halt its aging process, augment its repair, and promote recipient immune tolerance. Other recent advances include expanding the donor pool by reducing organ discard, and bioengineering and genetically modifying organs from other species to generate transplantable organs. Therapies discussed here will likely be most impactful if individualized on the basis of specific donor and recipient considerations.
    MeSH term(s) Humans ; Immunomodulation ; Immune Tolerance ; Bioengineering ; Graft Survival ; Organ Transplantation
    Language English
    Publishing date 2023-08-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207930-6
    ISSN 1545-326X ; 0066-4219
    ISSN (online) 1545-326X
    ISSN 0066-4219
    DOI 10.1146/annurev-med-050522-034012
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  3. Article ; Online: Negative Vaccination Strategies for Promotion of Transplant Tolerance.

    Tunbridge, Matthew J / Luo, Xunrong / Thomson, Angus W

    Transplantation

    2024  

    Abstract: Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without ... ...

    Abstract Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without compromising host responses to infection or enhancing the risk of malignant disease is a major goal in transplantation. One promising approach to achieve this goal is based on the concept of "negative vaccination." Vaccination (or actively acquired immunity) involves the presentation of both a foreign antigen and immunostimulatory adjuvant to the immune system to induce antigen-specific immunity. By contrast, negative vaccination, in the context of transplantation, involves the delivery of donor antigen before or after transplantation, together with a "negative adjuvant" to selectively inhibit the alloimmune response. This review will explore established and emerging negative vaccination strategies for promotion of organ or pancreatic islet transplant tolerance. These include donor regulatory myeloid cell infusion, which has progressed to early-phase clinical trials, apoptotic donor cell infusion that has advanced to nonhuman primate models, and novel nanoparticle antigen-delivery systems.
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004911
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    Zs.A 488: Show issues Location:
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  4. Article ; Online: Standardization and Interpretation of RNA-sequencing for Transplantation.

    Thareja, Gaurav / Suryawanshi, Hemant / Luo, Xunrong / Muthukumar, Thangamani

    Transplantation

    2023  Volume 107, Issue 10, Page(s) 2155–2167

    Abstract: RNA-sequencing (RNA-seq) is a technique to determine the order of nucleotides in an RNA segment. Modern sequencing platforms simultaneously sequence millions of RNA molecules. Advances in bioinformatics have allowed us to collect, store, analyze, and ... ...

    Abstract RNA-sequencing (RNA-seq) is a technique to determine the order of nucleotides in an RNA segment. Modern sequencing platforms simultaneously sequence millions of RNA molecules. Advances in bioinformatics have allowed us to collect, store, analyze, and disseminate data from RNA-seq experiments and decipher biological insights from large sequencing datasets. Although bulk RNA-seq has significantly advanced our understanding of tissue-specific gene expression and regulation, recent advances in single-cell RNA-seq have allowed such information to be mapped to individual cells, thus remarkably enhancing our insight into discrete cellular functions within a biospecimen. These different RNA-seq experimental approaches require specialized computational tools. Herein, we will first review the RNA-seq experimental workflow, discuss the common terminologies used in RNA-seq, and suggest approaches for standardization across multiple studies. Next, we will provide an up-to-date appraisal of the applications of bulk RNA-seq and single-cell/nucleus RNA-seq in preclinical and clinical research on kidney transplantation, as well as typical bioinformatic workflows utilized in such analysis. Lastly, we will deliberate on the limitations of this technology in transplantation research and briefly summarize newer technologies that could be combined with RNA-seq to permit more powerful dissections of biological functions. Because each step in RNA-seq workflow has numerous variations and could potentially impact the results, as conscientious citizens of the research community, we must strive to continuously modernize our analytical pipelines and exhaustively report their technical details.
    MeSH term(s) High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, RNA/methods ; Computational Biology/methods ; RNA/genetics ; Reference Standards ; Single-Cell Analysis
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004558
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  5. Article ; Online: Conversion of CD73hiFR4hi anergic T cells to IFN-γ-producing effector cells disrupts established immune tolerance.

    Dangi, Anil / Husain, Irma / Jordan, Collin Z / Yu, Shuangjin / Luo, Xunrong

    The Journal of clinical investigation

    2023  Volume 133, Issue 5

    MeSH term(s) T-Lymphocytes ; Clonal Anergy ; Immune Tolerance ; Lymphocytes
    Language English
    Publishing date 2023-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI163872
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  6. Article ; Online: Conversion of CD73hiFR4hi anergic T cells to IFN-γ–producing effector cells disrupts established immune tolerance

    Anil Dangi / Irma Husain / Collin Z. Jordan / Shuangjin Yu / Xunrong Luo

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 5

    Keywords Immunology ; Transplantation ; Medicine ; R
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Apoptotic Donor Cells in Transplantation.

    Husain, Irma / Luo, Xunrong

    Frontiers in immunology

    2021  Volume 12, Page(s) 626840

    Abstract: Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft survival, detrimental medication side effects to both the recipient and transplanted ... ...

    Abstract Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft survival, detrimental medication side effects to both the recipient and transplanted organ together with risks for opportunistic infections. Transplantation tolerance has so far only been achieved through hematopoietic chimerism, which carries with it a serious and life-threatening risk of graft versus host disease, along with variability in persistence of chimerism and uncertainty of sustained tolerance. More recently, numerous
    MeSH term(s) Animals ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/transplantation ; Apoptosis ; Cell- and Tissue-Based Therapy/methods ; Chimerism ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Graft vs Host Disease/immunology ; Graft vs Host Disease/prevention & control ; Humans ; Immunosuppressive Agents/therapeutic use ; Organ Transplantation ; Tissue Donors ; Transplantation Immunology ; Transplantation Tolerance ; Ureohydrolases/immunology
    Chemical Substances Immunosuppressive Agents ; Ureohydrolases (EC 3.5.3.-) ; allantoicase (EC 3.5.3.4)
    Language English
    Publishing date 2021-02-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.626840
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  8. Article ; Online: Discovery of Novel Hybrids of Edaravone and 6-phenyl-4,5-dihydropyridazin-3(2H)-one with Antiplatelet Aggregation and Neuroprotection for Ischemic Stroke Treatment.

    Li, Yi / He, Jieying / Luo, Bilan / Yu, Qinyang / Cai, Ting / Li, Yong / Fan, Lingling / Zhou, Xunrong / Tang, Lei

    Chemistry & biodiversity

    2024  , Page(s) e202400110

    Abstract: Drugs with anti-platelet aggregation and neuroprotection are of great significance for the treatment of ischemic stroke. A series of edaravone and 6-phenyl-4,5-dihydropyridazin-3(2H)-one hybrids were designed and synthesized. Among them, 6g showed the ... ...

    Abstract Drugs with anti-platelet aggregation and neuroprotection are of great significance for the treatment of ischemic stroke. A series of edaravone and 6-phenyl-4,5-dihydropyridazin-3(2H)-one hybrids were designed and synthesized. Among them, 6g showed the most effective cytoprotective effect against oxygen-glucose deprivation/reoxygenation-induced damage in BV2 cells and an excellent inhibitory effect on platelet aggregation induced by adenosine diphosphate and arachidonic acid. Additionally, 6g could prevent thrombosis caused by ferric chloride in rats and pose a lower risk of causing bleeding compared with aspirin. It provides better protection against ischemia/reperfusion injury in rats compared with edaravone and alleviates the oxidative stress related to cerebral ischemia/reperfusion by increasing the GSH and SOD levels and decreasing the MDA concentration. Finally, molecular docking results showed that 6g probably acts on PDE3 A and plays an anti-platelet aggregation effect. Overall, 6g could be a potential candidate compound for the treatment of ischemic stroke.
    Language English
    Publishing date 2024-02-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2139001-0
    ISSN 1612-1880 ; 1612-1872
    ISSN (online) 1612-1880
    ISSN 1612-1872
    DOI 10.1002/cbdv.202400110
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  9. Article ; Online: Dissecting the human kidney allograft transcriptome: single-cell RNA sequencing.

    Varma, Elly / Luo, Xunrong / Muthukumar, Thangamani

    Current opinion in organ transplantation

    2021  Volume 26, Issue 1, Page(s) 43–51

    Abstract: Purpose of review: Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the ... ...

    Abstract Purpose of review: Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the relevant biomedical literature.
    Recent findings: Sequencing is a technique to determine the order of nucleotides in a segment of RNA or DNA. RNA-seq of kidney allograft tissues has revealed novel mechanistic insights but does not provide information on individual cell types and cell states. scRNA-seq enables to study the transcriptome of individual cells and assess the transcriptional differences and similarities within a population of cells. Initial studies on rejecting kidney allograft tissues in humans have identified the transcriptional profile of the active players of the innate and adaptive immune system. Application of scRNA-seq in a preclinical model of kidney transplantation has revealed that allograft-infiltrating myeloid cells follow a trajectory of differentiation from monocytes to proinflammatory macrophages and exhibit distinct interactions with kidney allograft parenchymal cells; myeloid cell expression of Axl played a major role in promoting intragraft myeloid cell and T-cell differentiation.
    Summary: The current review discusses the technical aspects of scRNA-seq and summarizes the application of this technology to dissect the human kidney allograft transcriptome.
    MeSH term(s) Allografts ; Biomarkers/metabolism ; Graft Rejection/metabolism ; Humans ; Kidney/immunology ; Kidney Transplantation ; Macrophages/metabolism ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Transcriptome/immunology ; Transplantation, Homologous
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-01-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1390429-2
    ISSN 1531-7013 ; 1087-2418
    ISSN (online) 1531-7013
    ISSN 1087-2418
    DOI 10.1097/MOT.0000000000000840
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    Zs.A 5609: Show issues Location:
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  10. Article ; Online: AXL inhibition suppresses early allograft monocyte-to-macrophage differentiation and prolongs allograft survival.

    Jordan, Collin Z / Tunbridge, Matthew / Husain, Irma / Kitai, Hiroki / Dilts, Miriam E / Fay, Olivia K / Abe, Koki / Xiang, Catherine / Kwun, Jean / Souma, Tomokazu / Thorp, Edward B / Luo, Xunrong

    JCI insight

    2024  Volume 9, Issue 5

    Abstract: Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory ... ...

    Abstract Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages to promote allograft inflammation. However, factors that drive their differentiation to inflammatory macrophages are not understood. Here, we show that the receptor tyrosine kinase AXL was a key driver of early intragraft differentiation of recipient infiltrating monocytes to inflammatory macrophages in the presence of allogeneic stimulation and cell-to-cell contact. In this context, the differentiated inflammatory macrophages were capable of efficient alloantigen presentation and allostimulation of T cells of the indirect pathway. Consequently, early and transient AXL inhibition with the pharmacological inhibitor bemcentinib resulted in a profound reduction of initial allograft inflammation and a significant prolongation of allograft survival in a murine heart transplant model. Our results support further investigation of AXL inhibition as part of an induction regimen for transplantation.
    MeSH term(s) Mice ; Animals ; Monocytes ; Macrophages ; Transplantation, Homologous ; Allografts ; Inflammation
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.178502
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