Autoimmune arthritis induces paired immunoglobulin‐like receptor B expression on CD4<sup>+</sup> T cells from SKG mice

Rothe, Kathrin; Raulien, Nora; Köhler, Gabriele; Pierer, Matthias; Quandt, Dagmar; Wagner, Ulf

doi:10.1002/eji.201646747

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…Our present work provides the first proof of concept that ILT3.Fc suppresses autoimmune responses to neuroantigens in an experimental model of MS. The mechanism of action of ILT3.Fc in EAE this hypothesis are other authors' findings that high expression of PIR-B was associated with a milder course of arthritis in SKG mice, indicating the role of PIR-B in suppression of autoreactivity (51). The regulatory function of CD8 T cells is also supported by other authors' studies (28)(29)(30).…”

Section: Discussionsupporting

confidence: 66%

Suppression of Experimental Autoimmune Encephalomyelitis by ILT3.Fc

Lin

et al. 2021

The Journal of Immunology

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Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS that is characterized by demyelination, axonal loss, gliosis, and inflammation. The murine model of MS is the experimental autoimmune encephalopathy (EAE) induced by immunization of mice with myelin oligodendrocyte glycoprotein (MOG)35–55. Ig-like transcript 3 (ILT3) is an inhibitory cell surface receptor expressed by tolerogenic human dendritic cells. In this study, we show that the recombinant human ILT3.Fc protein binds to murine immune cells and inhibits the release of proinflammatory cytokines that cause the neuroinflammatory process that result in paralysis. Administration of ILT3.Fc prevents the rapid evolution of the disease in C57BL/6 mice and is associated with a profound reduction of proliferation of MOG35–55–specific Th1 and Th17 cells. Inhibition of IFN-γ and IL-17A in mice treated with ILT3.Fc is associated with delayed time of onset of the disease and its evolution to a peak clinical score. Neuropathological analysis shows a reduction in inflammatory infiltrates and demyelinated areas in the brains and spinal cords of treated mice. These results indicate that inhibition of Th1 and Th17 development provides effective suppression of EAE and suggests the feasibility of a clinical approach based on the use of ILT3.Fc for treatment of MS. Furthermore, our results open the way to further studies on the effect of the human ILT3.Fc protein in murine experimental models of autoimmunity and cancer.

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Section: Discussionsupporting

confidence: 66%

Suppression of Experimental Autoimmune Encephalomyelitis by ILT3.Fc

Lin

et al. 2021

The Journal of Immunology

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“…SKG mice harbour a spontaneous mutation in the protein kinase ZAP-70, which causes self-reactive T cells to escape negative selection in the thymus, thereby leading to T cell-mediated arthritis (Rothe et al, 2017; Guerard et al, 2016b). The arthrogenicity of the ZAP-70 mutation seems independent of genetic background (Guerard et al, 2016a).…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Cardiac phenotype in mouse models of systemic autoimmunity

Sanghera

Wong

Panahi

et al. 2019

Disease Models &Amp; Mechanisms

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Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity.

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“…Autoreactive T cells play an essential role in immune-mediated diseases including type 1 diabetes mellitus, 1 autoimmune arthritis, 2 multiple sclerosis 3,4 and psoriasis. 5 Keyhole limpet haemocyanin (KLH) is a metalloprotein considered to be a suitable immunization antigen for studying cellmediated immune responses.…”

Section: Introductionmentioning

confidence: 99%

“…Autoreactive T cells play an essential role in immune‐mediated diseases including type 1 diabetes mellitus, 1 autoimmune arthritis, 2 multiple sclerosis 3,4 and psoriasis 5 . Novel immunomodulatory drugs targeting the adaptive immune system and specifically T cells are often investigated in healthy subjects as part of the development program.…”

Section: Introductionmentioning

confidence: 99%

A randomized controlled trial with a delayed‐type hypersensitivity model using keyhole limpet haemocyanin to evaluate adaptive immune responses in man

Saghari

Gal

Ziagkos

et al. 2020

Brit J Clinical Pharma

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Keyhole limpet haemocyanin (KLH) immunization is a clinical model for the evaluation of human antibody responses. The current study evaluated the anti-KLH antibody response after KLH immunization and the delayed-type hypersensitivity response following intradermal KLH administration, using objective imaging techniques. Methods: Healthy male subjects aged 24.5 ± 5.4 years were randomized to intramuscular immunization with 100 μg KLH (n = 12) or placebo (n = 3). Anti-KLH antibody (Ig) M and IgG titres were determined before and every 7 days after KLH immunization for a total of 28 days. Twenty-one days after the immunization, all subjects received 1 μg KLH intradermally. Prior to and 2 days after intradermal KLH administration, skin blood perfusion, erythema and oedema were quantified using noninvasive imaging tools. Repeated measures ANCOVAs were used to analyse data. Results: Anti-KLH IgM and IgG titres increased after KLH immunization compared to placebo (estimated difference [ED]: 37%, 95% confidence interval [CI]: 19-51% and ED: 68%, 95% CI: 56-76% respectively). Upon intradermal KLH administration an increase in skin blood perfusion (ED: 10.9 arbitrary units (AU), 95% CI: 1.4-20.4 AU) and erythema (ED: 0.3 AU, 95% CI: 0.1-0.5 AU) was observed in KLH-immunized subjects compared to placebo. Conclusion: KLH immunization followed by intradermal KLH administration resulted in increased anti-KLH IgM and IgG titres and a delayed-type hypersensitivity response quantified by an increase in skin blood perfusion and erythema. Using noninvasive imaging tools the KLH model has the potential to serve as an objective tool to study the pharmacodynamics of T-cell-directed immunomodulatory drugs.

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Autoimmune arthritis induces paired immunoglobulin‐like receptor B expression on CD4⁺ T cells from SKG mice

Cited by 6 publications

References 47 publications

Suppression of Experimental Autoimmune Encephalomyelitis by ILT3.Fc

Suppression of Experimental Autoimmune Encephalomyelitis by ILT3.Fc

Cardiac phenotype in mouse models of systemic autoimmunity

A randomized controlled trial with a delayed‐type hypersensitivity model using keyhole limpet haemocyanin to evaluate adaptive immune responses in man

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Autoimmune arthritis induces paired immunoglobulin‐like receptor B expression on CD4+ T cells from SKG mice

Cited by 6 publications

References 47 publications

Suppression of Experimental Autoimmune Encephalomyelitis by ILT3.Fc

Suppression of Experimental Autoimmune Encephalomyelitis by ILT3.Fc

Cardiac phenotype in mouse models of systemic autoimmunity

A randomized controlled trial with a delayed‐type hypersensitivity model using keyhole limpet haemocyanin to evaluate adaptive immune responses in man

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Product

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Autoimmune arthritis induces paired immunoglobulin‐like receptor B expression on CD4⁺ T cells from SKG mice