Immunological aspects of allogeneic pancreatic islet transplantation: a comparison between mouse and human

Montanari, Elisa; Gonelle‐Gispert, Carmen; Knöll, Martin; Bottino, Rita; Bühler, Léo H.

doi:10.1111/tri.13445

Cited by 8 publications

(5 citation statements)

References 82 publications

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“…The problem, however, is still obtaining cells for transplantation, as well as their protection against destruction processes after transplantation [56][57][58][59]. Recently, an extensive discussion of methods for harvesting cells in animal models has also been presented [60,61]. The use of both pancreatic and islet transplants is limited due to the small number of deceased donors.…”

Section: Pancreas Transplantsmentioning

confidence: 99%

Type 1 diabetes – What’s new in prevention and therapeutic strategies?

Pilśniak,

Otto-Buczkowska

2023

pedm

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Type 1 diabetes (T1D) is an autoimmune disorder, and insulin deficiency is the result of β-cell dysfunction. Treatment of type 1 diabetes requires constant parenteral insulin administration, which can be very burdensome for the patient. Meticulous use of insulin therapy does not protect the patient against complications. Hence, the search for other methods of treatment as well as ways of preventing the onset of diabetes has been ongoing for a long time. The main obstacle in the implementation of the prevention task is the need to identify people at risk of developing diabetes before the start of autoimmunity. It seems that primary prevention is still unrealistic at the moment, because we do not know all the factors leading to the activation of autoimmunity processes. Research on the use of late secondary prevention in people who develop glucose tolerance disorders or in the early period after the onset of type 1 diabetes are at the most advanced stage. Gene therapy is another attempt at an alternative treatment and prevention of type 1 diabetes and still requires further research. Recent years have brought a lot of information about the nature of type 1 diabetes and the mechanisms leading to its development. However, it has not yet been established what factors decide about the initiation of autoimmunity and what determines the dynamics of these processes.

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Section: Pancreas Transplantsmentioning

confidence: 99%

Type 1 diabetes – What’s new in prevention and therapeutic strategies?

Pilśniak,

Otto-Buczkowska

2023

pedm

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“…After islet allotransplantation, once the immune system is activated, macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells migrate into the graft, drive the proinflammatory cascade and destroy the graft (8,9). As a result, the therapeutic efficacy of islet transplantation has also been largely limited by immune rejection.…”

Section: Introductionmentioning

confidence: 99%

“…Antigens of donor islet grafts, such as insulin, insulinomaassociated protein-2, glutamate decarboxylase, and zinc transporter 8, activate DCs and macrophages, which subsequently activate T cells and B cells (9). These antigens are recognized by the host immune system through the direct or indirect presentation.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft

Chen

Yao²,

Lu³

et al. 2022

Front. Immunol.

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Islet transplantation to treat the late stage of type 1 diabetic patient (T1DM) has recently made inspiring success in clinical trials. However, most patients experience a decline in islet graft function in one to three years due to immune rejection. Although the mechanisms of immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells, that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts and syngeneic grafts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the complexity of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in the mouse model of islet transplantation. Our data revealed T lymphocytes and myeloid cells as the main immune components of grafts 7 days post-islet transplantation, especially in allografts. Moreover, our results indicated that allogeneic islet cells were transformed into antigen-presenting cell-like cells with highly expressed MHC class I molecules and genes involved in MHC class I-mediated antigen presentation. This transformation may dramatically facilitate the interaction with cytotoxic CD8+ T cells and promote the destruction of islet allografts. Our study provides insight into the transcriptomics and diverse microenvironment of islet grafts and their impacts on immune rejection.

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“…Studies to advance islet transplantation in mice would benefit from newer models of experimental diabetes 1 . The most widely-used models are those involving administration of islet β cell toxins, like streptozotocin (STZ) 2 .…”

Section: Introductionmentioning

confidence: 99%

Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes

Bhagchandani

Chang

Zhao

et al. 2022

Sci Rep

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Improved models of experimental diabetes are needed to develop cell therapies for diabetes. Here, we introduce the B6 RIP-DTR mouse, a model of experimental diabetes in fully immunocompetent animals. These inbred mice harbor the H2b major histocompatibility complex (MHC), selectively express high affinity human diphtheria toxin receptor (DTR) in islet β-cells, and are homozygous for the Ptprca (CD45.1) allele rather than wild-type Ptprcb (CD45.2). 100% of B6 RIP-DTR mice rapidly became diabetic after a single dose of diphtheria toxin, and this was reversed indefinitely after transplantation with islets from congenic C57BL/6 mice. By contrast, MHC-mismatched islets were rapidly rejected, and this allotransplant response was readily monitored via blood glucose and graft histology. In peripheral blood of B6 RIP-DTR with mixed hematopoietic chimerism, CD45.2 BALB/c donor blood immune cells were readily distinguished from host CD45.1 cells by flow cytometry. Reliable diabetes induction and other properties in B6 RIP-DTR mice provide an important new tool to advance transplant-based studies of islet replacement and immunomodulation to treat diabetes.

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Immunological aspects of allogeneic pancreatic islet transplantation: a comparison between mouse and human

Cited by 8 publications

References 82 publications

Type 1 diabetes – What’s new in prevention and therapeutic strategies?

Type 1 diabetes – What’s new in prevention and therapeutic strategies?

Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft

Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes

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