PVG rats, resistant to experimental allergic thyroiditis, develop high serum levels of thyroglobulin after sensitization

Eishi, Yoshinobu; McCullagh, Peter

doi:10.1016/0090-1229(88)90099-2

Cited by 6 publications

(2 citation statements)

References 11 publications

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“…From previous studies, inbred rat strains have shown to differ in susceptibility to various models of human immune-mediated and inflammatory diseases. The Dark Agouti (DA) rats have previously been studied in experimental autoimmune diseases such as arthritis and encephalomyelitis due to their high susceptibility to develop long-lasting immune-mediated disorders (Gasser et al, 1973; Griffiths et al, 1981; Battisto et al, 1982; Eishi and McCullagh, 1988). …”

Section: Introductionmentioning

confidence: 99%

Lung exposure of titanium dioxide nanoparticles induces innate immune activation and long-lasting lymphocyte response in the Dark Agouti rat

Gustafsson

Lindstedt²,

Elfsmark

et al. 2011

Journal of Immunotoxicology

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Nanomaterial of titanium dioxide (TiO2) is manufactured in large-scale production plants, resulting in risks for accidental high exposures of humans. Inhalation of metal oxide nanoparticles in high doses may lead to both acute and long-standing adverse effects. By using the Dark Agouti (DA) rat, a strain disposed to develop chronic inflammation following exposure to immunoactivating adjuvants, we investigated local and systemic inflammatory responses after lung exposure of nanosized TiO2 particles up to 90 days after intratracheal instillation. TiO2 induced a transient response of proinflammatory and T-cell-activating cytokines (interleukin [IL]-1α, IL-1β, IL-6, cytokine-induced neutrophil chemoattractant [CINC]-1, granulocyte-macrophage colony-stimulating factor [GM-CSF], and IL-2) in airways 1-2 days after exposure, accompanied byaninfluxofeosinophilsand neutrophils. Neutrophil numbers remained elevated for 30 days, whereas the eosinophils declined to baseline levels at Day 8, simultaneously with an increase of dendritic cells and natural killer (NK) cells. The innate immune activation was followed by a lymphocyte expansion that persisted throughout the 90-day study. Lymphocytes recruited to the lungs were predominantly CD4+ helper T-cells, but we also demonstrated presence of CD8+T-cells, B-cells, and CD25+T-cells. In serum, we detected both an early cytokine expression at Days 1-2 (IL-2, IL-4, IL-6, CINC-1, IL-10, and interferon-gamma [IFN-γ] and a second response at Day 16 of tumor necrosis factor-alpha (TNF-α), indicating systemic late-phase effects in addition to the local response in airways. In summary, these data demonstrate a dynamic response to TiO2 nanoparticles in the lungs of DA rats, beginning with an innate immune activation of eosinophils, neutrophils, dendritic cells, and NK cells, followed by a long-lasting activation of lymphocytes involved in adaptive immunity. The results have implications for the assessment of risks for adverse and persistent immune stimulation following nanoparticle exposures in sensitive populations.

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Section: Introductionmentioning

confidence: 99%

Lung exposure of titanium dioxide nanoparticles induces innate immune activation and long-lasting lymphocyte response in the Dark Agouti rat

Gustafsson

Lindstedt²,

Elfsmark

et al. 2011

Journal of Immunotoxicology

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“…For example, in an animal model of experimental autoimmune thyroiditis, the subcutaneous immunization of healthy animals with thyroglobulin using complete Freund’s adjuvant induces lymphocytic thyroiditis that simulates Hashimoto’s disease. In this animal model, DA strain rats are high responders and PVG strain rats are low responders; serum antibody titers to thyroglobulin are elevated in both DA and PVG rats, but lymphocytic thyroiditis occurs only in DA rats [ 59 ]. Such disease susceptibility of the host’s immune system [ 60 ] and dissociation of humoral and cellular immune responses to an identical antigen are also observed in sarcoidosis patients if C. acnes is assumed to be an intracellular antigen like the organ-specific autoantigen.…”

Section: Allergic Cellular Immune Response To Autoantigensmentioning

confidence: 99%

Potential Association of Cutibacterium acnes with Sarcoidosis as an Endogenous Hypersensitivity Infection

Eishi

2023

Microorganisms

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The immunohistochemical detection of Cutibacterium acnes in sarcoid granulomas suggests its potential role in granuloma formation. C. acnes is the sole microorganism ever isolated from sarcoid lesions. Histopathologic analysis of some sarcoid lymph nodes reveals latent infection and intracellular proliferation of cell-wall-deficient C. acnes followed by insoluble immune-complex formation. Activation of T helper type 1 (Th1) immune responses by C. acnes is generally higher in sarcoidosis patients than in healthy individuals. Pulmonary granulomatosis caused by an experimental adjuvant-induced allergic immune response to C. acnes is preventable by antimicrobials, suggesting that the allergic reaction targets C. acnes commensal in the lungs. C. acnes is the most common bacterium detected intracellularly in human peripheral lungs and mediastinal lymph nodes. Some sarcoidosis patients have increased amounts of C. acnes-derived circulating immune complexes, which suggests the proliferation of C. acnes in affected organs. In predisposed individuals with hypersensitive Th1 immune responses to C. acnes, granulomas may form to confine the intracellular proliferation of latent C. acnes triggered by certain host-related or drug-induced conditions. Current clinical trials in patients with cardiac sarcoidosis are evaluating combined treatment with steroids and antimicrobials during active disease with continued antimicrobial therapy while tapering off steroids after the disease subsides.

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The Physiological Role of Regulatory T Cells in the Prevention of Autoimmunity: Generation, Specificity and Mode of Action

Seddon¹

2001

Autoimmunity

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PVG rats, resistant to experimental allergic thyroiditis, develop high serum levels of thyroglobulin after sensitization

Cited by 6 publications

References 11 publications

Lung exposure of titanium dioxide nanoparticles induces innate immune activation and long-lasting lymphocyte response in the Dark Agouti rat

Lung exposure of titanium dioxide nanoparticles induces innate immune activation and long-lasting lymphocyte response in the Dark Agouti rat

Potential Association of Cutibacterium acnes with Sarcoidosis as an Endogenous Hypersensitivity Infection

The Physiological Role of Regulatory T Cells in the Prevention of Autoimmunity: Generation, Specificity and Mode of Action

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