CD95 and CD95-ligand expression in endocrine pancreas of NOD, NOR and BALB/c mice

Signore, Alberto; Annovazzi, Alessio; Procaccini, Enrica; Beales, P. E.; Spencer, Jo; Testi, Roberto; Ruberti, Giovina

doi:10.1007/s001250050852

Cited by 23 publications

(20 citation statements)

References 9 publications

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“…Fas was not detected in rat islet ␤ cells during the postnatal period or in young adult mice, including NOD, in agreement with our data (Hanke, 2000;Signore et al, 1997;Thomas et al, 1999). Neurons and Schwann cells can express both Fas and FasL, and this coexpression is thought Immunohistochemistry for Bcl-2 in control and NODscid pancreata during the early postnatal period.…”

Section: Innervation In Neonatal Mousesupporting

confidence: 93%

“…In rat islets, FasL was detected during the first 3 days of life and disappeared thereafter (Hanke, 2000). In young adult control and NOD mice, FasL was not observed in islet ␤ cells (Thomas et al, 1999) but was observed in surrounding ␣ cells (Signore et al, 1997). Our observations confirm the absence of FasL expression in mouse ␤ cells under normal conditions.…”

Section: Innervation In Neonatal Mousesupporting

confidence: 79%

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Proapoptosis and Antiapoptosis-Related Molecules During Postnatal Pancreas Development in Control and Nonobese Diabetic Mice: Relationship with Innervation

Durant

Geutskens

Blokland

et al. 2003

Laboratory Investigation

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SUMMARY:The mouse pancreas, an immature organ at birth, reaches its adult size and morphology after weaning (3 weeks of age). Around this time, apoptotic phenomena and various types of macrophages are normally present. During development, Fas-Fas ligand (FasL) interactions are known to play a role in apoptotic events involved in tissue remodeling and elimination of damaged cells, and macrophages are routinely observed near apoptotic cells. Apoptosis and Fas-FasL interactions are also thought to be involved in the pathogenesis of autoimmune diseases, particularly type 1 diabetes (T1D). Therefore, we used early postnatal mouse pancreata from three control strains (C57BL/6, DBA/2, BALB/c) and from two strains with the nonobese diabetic (NOD)-related genetic background (the spontaneous T1D NOD model and the lymphocyte-deficient NODscid strain) to study apoptotic phenomena together with the molecular and immunohistochemical expression of proapoptosis (Fas, FasL) and antiapoptosis (Bcl-2) proteins. First, although no major difference in the numbers of total pancreatic apoptotic cells was noted among strains, significantly more FasL ϩ expression was detected immunohistochemically in mice with the NOD genetic background than in control pancreata from birth to 1 month of age. Second, FasL ϩ , Fas ϩ , and Bcl-2 ϩ structures seemed to be associated with innervation, regardless of the strain and age. Third, in control and NOD strains, nerves (identified by immunohistochemical labeling of peripherin or neurofilament 200), were often observed in periductular and peri-insular areas. Finally, some peripherin-positive nerves expressed the interferon-inducible protein-10 chemokine, and various types of macrophages were found to be in close proximity. These data highlight an overlooked, innervation-related aspect of normal mouse postnatal pancreas development with possible implications in T1D pathogenesis. (Lab Invest 2003, 83:227-239).

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Section: Innervation In Neonatal Mousesupporting

confidence: 93%

Section: Innervation In Neonatal Mousesupporting

confidence: 79%

Proapoptosis and Antiapoptosis-Related Molecules During Postnatal Pancreas Development in Control and Nonobese Diabetic Mice: Relationship with Innervation

Durant

Geutskens

Blokland

et al. 2003

Laboratory Investigation

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show abstract

“…According to our experiments (Fig. 2 and data not shown) and the experience of others (38,42,43), murine -cells express FasL neither spontaneously nor after exposure to pro-inflammatory cytokines, excluding the possibility of suicide/fratricide triggered by Fas:FasL interactions. However, these results are contrasted by a recent report by SuarezPinzon et al (44), which found FasL expression on a minority of R2D6 + islet cells of NOD mice.…”

Section: Discussionsupporting

confidence: 54%

Nitric oxide production and Fas surface expression mediate two independent pathways of cytokine-induced murine beta-cell damage.

2000

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“…The fact that diabetogenic CD4 + T cells spare α cells and other endocrine islet cells cannot be taken as an argument against a role for Fas in β-cell lysis by CD4 + T cells; these other islet cells may be resistant to Fas-mediated cell death. In fact, IL-1 has been shown to selectively induce Fas expression on β cells but not on other endocrine cells (26,27), and α cells express FasL, but not Fas (47).…”

mentioning

confidence: 99%

IL-1α, IL-1β, and IFN-γ mark β cells for Fas-dependent destruction by diabetogenic CD4+ T lymphocytes

Amrani¹,

Verdaguer²,

Thiessen³

et al. 2000

J. Clin. Invest.

128

101

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Cytokines such as IL-1α, IL-1β, and IFN-γ have long been implicated in the pathogenesis of autoimmune diabetes, but the mechanisms through which they promote diabetogenesis remain unclear. Here we show that CD4 + T lymphocytes propagated from transgenic nonobese diabetic (NOD) mice expressing the highly diabetogenic, β cell-specific 4.1-T-cell receptor (4.1-TCR) can kill IL-1α-, IL-1β-, and IFN-γ-treated β cells from NOD mice. Untreated NOD β cells and cytokine-treated β cells from Fas-deficient NOD.lpr mice are not targeted by these T cells. Killing of islet cells in vitro was associated with cytokine-induced upregulation of Fas on islet cells and was independent of MHC class II expression. Abrogation of Fas expression in 4.1-TCR-transgenic NOD mice afforded nearly complete protection from diabetes and did not interfere with the development of the transgenic CD4 + T cells or with their ability to cause insulitis. In contrast, abrogation of perforin expression did not affect β cell-specific cytotoxicity or the diabetogenic potential of these T cells. These data demonstrate a novel mechanism of action of IL-1α, IL-1β, and IFN-γ in autoimmune diabetes, whereby these cytokines mark β cells for Fas-dependent lysis by autoreactive CD4 + T cells.

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CD95 and CD95-ligand expression in endocrine pancreas of NOD, NOR and BALB/c mice

Cited by 23 publications

References 9 publications

Proapoptosis and Antiapoptosis-Related Molecules During Postnatal Pancreas Development in Control and Nonobese Diabetic Mice: Relationship with Innervation

Proapoptosis and Antiapoptosis-Related Molecules During Postnatal Pancreas Development in Control and Nonobese Diabetic Mice: Relationship with Innervation

Nitric oxide production and Fas surface expression mediate two independent pathways of cytokine-induced murine beta-cell damage.

IL-1α, IL-1β, and IFN-γ mark β cells for Fas-dependent destruction by diabetogenic CD4+ T lymphocytes

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