Injection of CD40 DNA vaccine ameliorates the autoimmune pathology of non-obese diabetic mice with Sjögren’s syndrome

Zhou, Yicheng; Yuan, Xiang; Wang, Qikai; Zhang, Hong; Wang, Guosheng; Li, Xiang-Pei; Wang, Yiping; Harris, David C.H.; Li, Xiaomei

doi:10.1016/j.imlet.2020.07.005

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…NOD/ShiLtJ mice are commonly used as a type 1 diabetes model, as, depending on the conditions, approximately 50–80% of female NOD/ShiLtJ mice spontaneously develop type 1 diabetes. Moreover, these mice also display a propensity for polyautoimmunity, including a low incidence of autoimmune thyroiditis and Sjögren’s syndrome [ 42 ]. This was also confirmed in our study, as vehicle exposed NOD/ShiLtJ mice displayed low ANA positivity, while C57BL/6J mice did not exhibit ANA positivity under vehicle exposure.…”

Section: Discussionmentioning

confidence: 99%

Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles

Janssen,

Lemaire,

Marain

et al. 2024

Part Fibre Toxicol

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Background Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization. Results The findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains. Conclusion Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.

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Section: Discussionmentioning

confidence: 99%

Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles

Janssen,

Lemaire,

Marain

et al. 2024

Part Fibre Toxicol

View full text Add to dashboard Cite

show abstract

“…NOD/ShiLtJ mice are commonly used as a type 1 diabetes model, as, depending on the conditions, approximately 50–80% of female NOD/ShiLtJ mice spontaneously develop type 1 diabetes. Moreover, these mice also display a propensity for polyautoimmunity, including a low incidence of autoimmune thyroiditis and Sjögren’s syndrome ( 48 ). This was also confirmed in our study, as vehicle exposed NOD/ShiLtJ mice displayed low ANA positivity, while C57BL/6J mice did not exhibit ANA positivity under vehicle exposure.…”

Section: Discussionmentioning

confidence: 99%

Differential Pulmonary Toxicity and Autoantibody Formation in Genetically Distinct Mouse Strains Following Combined Exposure to Silica and Diesel Exhaust Particles

Janssen,

Lemaire,

Marain

et al. 2023

Preprint

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Background Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of silica and DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization. Results Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside limited fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. Conclusion Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of diesel exhaust particles on these silica-induced effects was minimal.

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“…Compared with the control group, NOD mice treated with the CD40 DNA vaccine showed reduced lymphocyte infiltration and increased salivary secretion in salivary glands. At the same time, the expression levels of TNF-α and IL-6 in salivary glands decreased, the number of dendritic cells and plasma cells decreased, and the ANA level decreased ( 211 ). Iscalimab, an anti-CD40 antibody, has been shown to be safe and well tolerated at all doses in phase I clinical studies, with no clinically relevant changes in any of the safety parameters, including no evidence of thromboembolic events ( 212 ).…”

Section: Treatmentmentioning

confidence: 99%

Composition and regulation of the immune microenvironment of salivary gland in Sjögren’s syndrome

Tan

Wang

2022

Front. Immunol.

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Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and inflammation. Patients often have dry mouth and dry eye symptoms, which seriously affect their lives. Improving dry mouth and eye symptoms has become a common demand from patients. For this reason, researchers have conducted many studies on external secretory glands. In this paper, we summarize recent studies on the salivary glands of pSS patients from the perspective of the immune microenvironment. These studies showed that hypoxia, senescence, and chronic inflammation are the essential characteristics of the salivary gland immune microenvironment. In the SG of pSS, genes related to lymphocyte chemotaxis, antigen presentation, and lymphocyte activation are upregulated. Interferon (IFN)-related genes, DNA methylation, sRNA downregulation, and mitochondrial-related differentially expressed genes are also involved in forming the immune microenvironment of pSS, while multiple signaling pathways are involved in regulation. We further elucidated the regulation of the salivary gland immune microenvironment in pSS and relevant, targeted treatments.

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Injection of CD40 DNA vaccine ameliorates the autoimmune pathology of non-obese diabetic mice with Sjögren’s syndrome

Cited by 6 publications

References 43 publications

Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles

Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles

Differential Pulmonary Toxicity and Autoantibody Formation in Genetically Distinct Mouse Strains Following Combined Exposure to Silica and Diesel Exhaust Particles

Composition and regulation of the immune microenvironment of salivary gland in Sjögren’s syndrome

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