Study Tells How Anti-dsDNA Antibodies Promote Lupus Severity

Study Tells How Anti-dsDNA Antibodies Promote Lupus Severity
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Researchers at Sun Yat-sen University in China have found that a group of anti-nuclear antibodies that target double stranded DNA, anti-dsDNA, may cause inflammation in systemic lupus erythomatosus (SLE) patients, through the activation of a particular molecular inflammasome.

The findings were revealed in the study “Anti-dsDNA antibodies bind to TLR4 and activate NLRP3 inflammasome in lupus monocytes/macrophages,” published in the Journal of Translational Medicine.

SLE is a systemic autoimmune disease that affects multiple organs in the body. Dysregulation of the immune system plays a crucial role in the development and progression of the disease. Interluekin-1 (IL-1β) is a proinflammatory cytokine extensively linked to SLE. Not only is it expressed in the anti-body rich blood of SLE patients, its depletion in mice causes resistance to the induction of experimental lupus.

The NLRP3 inflammasome is a mulltiprotien complex that when activated, leads to the production and secretion of the active form of IL-1β. Inflammasomes are expressed in monocytes and macrophages that are activated by infection signals that trigger the production of pro-inflammatory cytokines to boost the immune response.

Niansheng Yang and his team have shown that anti-dsDNA antibodies, found in the blood of SLE patients before disease onset and known to play a role in the pathogenesis of SLE, can stimulate the expression and secretion of IL-1β from mononuclear cells and monocytes through the activation of the NLRP3 inflammasome.

The results suggest that anti-dsDNA antibodies might promote disease initiation and progression by inducing IL-1β production and enhancing the inflammatory response in a NLRP3-dependent manner.

The  investigators also found that anti-dsDNA antibodies induced NLRP3 inflammasome activation by binding to TLR4, then induced the production of mitochondrial reactive oxygen species (ROS).

When anti-dsDNA antibodies were injected into an SLE mouse model, activation of the inflammasome in the monocytes was stimulated. The activation may be involved in the differentiation of Th17 cells, a newly identified subpopulation of CD4 T-cells that play major roles in SLE pathogenesis – because the mice presented increased levels of Th17 cells and decreased the amount of regulatory T cells.

These results suggest that anti-dsDNA antibodies-mediated NLRP3 activation may lead to increased disease severity by disrupting the balance of Th17/Treg cells.

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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