Murine metal-induced systemic autoimmunity: baseline and stimulated cytokine mRNA expression in genetically susceptible and resistant strains

Häggqvist, Bo; Hultman, Per

doi:10.1046/j.1365-2249.2001.01636.x

Cited by 27 publications

(29 citation statements)

References 44 publications

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“…15 The increase in IL-10 in Daf1-deficient mice with mHgIA was unexpected considering that IL-10 has been shown to suppress features of mHgIA in C57BL/6 mice 31 and to be increased in the mHgIA-resistant A.TL mouse. 33 IL-10 has been found to be decreased in Daf1-deficient C57BL/6 and BALB/c mice following OVA immunization and, unlike IFN-c and IL-2, the decrease in IL-10 is not influenced by the absence of complement. 3 This suggests that binding of complement to Daf1 does not mediate regulation of IL-10 and implicates an interaction with CD97, which binds at a different site on Daf1, 34 as a mediator of IL-10 regulation.…”

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confidence: 86%

Decay‐accelerating factor 1 (Daf1) deficiency exacerbates xenobiotic‐induced autoimmunity

et al. 2010

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Summary Absence of decay‐accelerating factor 1 (Daf1) has been shown to enhance T‐cell responses and autoimmunity via increased expression of specific cytokines, most notably interferon (IFN)‐γ. To determine if Daf1 deficiency can exacerbate IFN‐γ‐dependent murine mercury‐induced autoimmunity (mHgIA), C57/BL6 Daf1+/+ and Daf1−/− mice were exposed to mercuric chloride (HgCl2) and examined for differences in cytokine expression, T‐cell activation and features of humoral autoimmunity. In the absence of Daf1, mHgIA was exacerbated, with increased serum immunoglobulin G (IgG), anti‐nuclear autoantibodies (ANAs) and anti‐chromatin autoantibodies. This aggravated response could not be explained by increased T‐cell activation but was associated with increased levels of IFN‐γ, interleukin (IL)‐2, IL‐4 and IL‐10 but not IL‐17 in Daf1‐deficient mice. Anti‐CD3/anti‐CD28 costimulation of Daf1−/− CD4+ T cells in vitro was also found to increase cytokine expression, but the profile was different from that of mHgIA, suggesting that the cytokine changes observed in Daf1 deficiency reflect a response to mercury. The role of Daf1 in influencing cytokine expression was further examined by stimulation of CD4+ T cells in the presence of anti‐CD3 and CD97, a molecular partner for Daf1. This resulted in increased IL‐10, decreased IL‐17 and IL‐21 and decreased IFN‐γ. These findings demonstrate that the absence of Daf1 exacerbates mHgIA, with changes in the profile of expressed cytokines. Interaction between Daf1 and its molecular partner CD97 was found to modify expression of mHgIA‐promoting cytokines, suggesting a possible approach for the suppression of overaggressive cytokine production in autoimmunity.

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confidence: 86%

Decay‐accelerating factor 1 (Daf1) deficiency exacerbates xenobiotic‐induced autoimmunity

et al. 2010

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“…These results demonstrate that modulation of the level of Relationship between Daf1 and cytokine levels in CD4؉ T cells in mHgIA. Previous studies have determined that induction of mHgIA is dependent upon the presence of IFN␥ (19) and that established disease is associated with the presence of elevated IL-4 in lymphoid organs (19,30,31). To determine whether changes in Daf1 expression were associated with differences in cytokine expression, CD3ϩ,CD4ϩ splenocytes were sorted according to their expression of CD44 ( Figure 5A), and then real-time PCR was used to measure the levels of Daf1, IL-2, IL-4, and IFN␥ in the 2 populations.…”

Section: Unchanged Daf1 Expression On T Cells From Mhgia-resistant B1mentioning

confidence: 99%

Reduced expression of decay‐accelerating factor 1 on CD4+ T cells in murine systemic autoimmune disease

Cauvi

Pollard

2007

Arthritis & Rheumatism

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Objective. Deficiency of decay-accelerating factor 1 (termed Daf1 in mice) has been shown to exacerbate autoimmunity, and recent studies have suggested that this may be explained by Daf1 acting as a regulator of T cell immunity. The aim of this study was to determine whether Daf1 expression on T cells is modulated during development of autoimmunity in mice.Methods. To test this hypothesis, we examined Daf1 levels in NZB, DBA/2, and B10.S mice before and after induction of murine mercury-induced autoimmunity (mHgIA). Daf1 was measured by real-time polymerase chain reaction and flow cytometry, and levels of Daf1 were correlated with markers of lymphocyte activation and cytokine production.Results. Autoimmune-prone NZB mice had low endogenous levels of Daf1 irrespective of the induction of mHgIA. Induction of autoimmunity reduced Daf1 expression in mHgIA-sensitive B10.S mice, particularly on activated/memory (CD44 high ) CD4؉ T cells that accumulate as a result of exposure to mercury. Murine mercury-induced autoimmunity-resistant DBA/2 mice, which fail to accumulate CD44 high T cells, showed no change in Daf1 expression. Modulation of Daf1 expression was found to require CD4؉ T cell costimulation, since B10.S mice deficient in CD28 were unable to down-regulate Daf1 or accumulate activated/memory CD4؉ T cells. In B10.S mice exposed to mercury, the production of interleukin-4 (IL-4), but not that of IL-2 or interferon-␥, in the spleen was associated with CD44 high ,Daf1 low ,CD4؉ T cells. Conclusion. These findings demonstrate that reduction of Daf1 expression is closely associated with CD4؉ T cell activation and the accumulation of CD44 high (activated/memory),CD4؉ T cells in both spontaneous and induced systemic autoimmune disease.

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“…Mercury salts have been shown to affect cytokine production by triggering Ca 2+ signals and activating protein kinase C [34]. Mouse strains either sensitive or resistant to mercury were given an oral challenge of mercury(II) nitrate [35]. Increased mRNA expression of IL-2, IL-4, and IFN-γ occurred in the lymphoid tissue of sensitive mice, whereas IL-10 expression was increased and IL-2 and IFN-γ expression were decreased in the resistant mice.…”

Section: Immunosuppression and Immunostimulation In Rodentsmentioning

confidence: 99%

Immunological effects of mercury (IUPAC Technical Report)

Schwenk

Klein

Templeton

2009

Pure and Applied Chemistry

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Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted without the Immunological effects of mercury (IUPAC Technical Report)Abstract: Various chemical species of mercury differ considerably with regard to their route of absorption and their distribution in the body, yet many of them and their metabolites exhibit high-affinity binding to sulfanyl groups of proteins. Among all metals, mercury appears to have the most diverse effects on the immune system. Depending on the animal species and experimental conditions, mercury compounds may cause immunosuppression or immunostimulation, autoimmune reactions, or hypersensitivity. Mercury-sensitive strains of rats and mice are often used as model organisms to study the time course and events in autoimmunity. Within about 14 days after onset of oral mercury(II) exposure, levels of immunoglobulins E and G (IgE and IgG) increase, including autoantibodies to biomolecules such as laminin and fibrillarin. Antigen-antibody complexes are formed and are the cause of subsequent autoimmune diseases of blood vessels and organs. Mercury may induce local mercury hypersensitivity in humans, but the evidence for a role of mercury in autoimmune disease of humans is at best weak. Models for the immune effects of mercury are presented on the basis of current knowledge.

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Murine metal-induced systemic autoimmunity: baseline and stimulated cytokine mRNA expression in genetically susceptible and resistant strains

Cited by 27 publications

References 44 publications

Decay‐accelerating factor 1 (Daf1) deficiency exacerbates xenobiotic‐induced autoimmunity

Decay‐accelerating factor 1 (Daf1) deficiency exacerbates xenobiotic‐induced autoimmunity

Reduced expression of decay‐accelerating factor 1 on CD4+ T cells in murine systemic autoimmune disease

Immunological effects of mercury (IUPAC Technical Report)

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