Fas/Fas Ligand Interactions Play an Essential Role in the Initiation of Murine Autoimmune Diabetes

Nakayama, Maki; Nagata, Michio; Yasuda, Hisafumi; Arisawa, K; Kotani, Reiko; Yamada, Katsumi; Chowdhury, Shahead Ali; Chakrabarty, Sagarika; Jin, Zhen Zi; Yagita, Hideo; Yokono, Koichi; Kasuga, Masato

doi:10.2337/diabetes.51.5.1391

Cited by 40 publications

(40 citation statements)

References 38 publications

(31 reference statements)

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“…26,28,29 Thus, both genetic and pharmacological results directly related the higher presence of CD5 ϩ B cells in the pancreata of NOD mice to inhibition of FasL activity. In addition, consistent with previous results, 27 treatment with FasL-neutralizing mAb halted progression of insulitis in NOD-wt mice compared with control mice ( Figure 3B). …”

Section: Cd5 ϩ B Cells Constitute a Significant Proportion Of B Cellssupporting

confidence: 81%

“…More important, we found that antibody blockade of FasL protects NOD-wt mice from T1D without causing lymphoproliferation, thereby directly linking the protection to FasL blockade. 26,27 In addition, disease-resistant NOD-gld/ϩ mice harbor diabetogenic T cells that cause disease in NODsevere combined immunodeficiency adoptive hosts. 26 We hypothesize that inactivation of FasL leads to augmentation of an immunoregulatory mechanism that keeps the diabetogenic T cells in check.…”

mentioning

confidence: 99%

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Inhibition of Fas Ligand in NOD Mice Unmasks a Protective Role for IL-10 against Insulitis Development

Xiao

Mohamood

Uddin

et al. 2011

The American Journal of Pathology

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Section: Cd5 ϩ B Cells Constitute a Significant Proportion Of B Cellssupporting

confidence: 81%

mentioning

confidence: 99%

Inhibition of Fas Ligand in NOD Mice Unmasks a Protective Role for IL-10 against Insulitis Development

Xiao

Mohamood

Uddin

et al. 2011

The American Journal of Pathology

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“…In addition, the administration of anti-FasL antibody at 2-4 weeks of age to NOD mice prevented insulitis and diabetes. This suggests that Fas/FasL interactions contribute to CD4(þ) T-cell-mediated beta-cell destruction and play an essential role in the initiation of autoimmune diabetes (Nakayama et al, 2002).…”

Section: Pathways Of Caspase Activation In Apoptosismentioning

confidence: 99%

“…Indeed, Fas antibody, FasL antibody, or any other reagents that could decrease the expression and translocation of Fas could be used in blocking apoptosis of an islet. Nakayama et al (2002) demonstrated that administration of anti-FasL antibody at 2-4 weeks of age completely prevented insulitis and diabetes. High glucose-induced apoptosis is due to the interaction between the constitutively expressed FasL and the upregulated Fas.…”

Section: Blocking the Fas And Fasl Pathwaymentioning

confidence: 99%

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Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Hui

Dotta

Mario

et al. 2004

Journal Cellular Physiology

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The homeostatic control of beta-cell mass in normal and pathological conditions is based on the balance of proliferation, differentiation, and death of the insulinsecreting cells. A considerable body of evidence, accumulated during the last decade, has emphasized the significance of the disregulation of the mechnanisms regulating the apoptosis of beta-cells in the sequence of events that lead to the development of diabetes. The identification of agents capable of interfering with this process needs to be based on a better understanding of the beta-cell specific pathways that are activated during apoptosis. The aim of this article is fivefold: (1) a review of the evidence for beta-cell apoptosis in Type I diabetes, Type II diabetes, and islet transplantation, (2) to review the common stimuli and their mechanisms in pancreatic beta-cell apoptosis, (3) to review the role of caspases and their activation pathway in beta-cell apoptosis, (4) to review the caspase cascade and morphological cellular changes in apoptotic beta-cells, and (5) to highlight the putative strategies for preventing pancreatic beta-cells from apoptosis.

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The dual role of Fas-ligand as an injury effector and defense strategy in diabetes and islet transplantation

et al. 2006

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The exact process that leads to the eruption of autoimmune reactions against beta cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of beta cell injury is controversial and points to possibly important roles for the perforin-granzyme, Fas-Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of beta cells to FasL-mediated apoptosis, the conditions that underlie this beta cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of beta-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation.

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Fas/Fas Ligand Interactions Play an Essential Role in the Initiation of Murine Autoimmune Diabetes

Cited by 40 publications

References 38 publications

Inhibition of Fas Ligand in NOD Mice Unmasks a Protective Role for IL-10 against Insulitis Development

Inhibition of Fas Ligand in NOD Mice Unmasks a Protective Role for IL-10 against Insulitis Development

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

The dual role of Fas-ligand as an injury effector and defense strategy in diabetes and islet transplantation

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