Skin inflammation induced by lupus serum was inhibited in IL-1R deficient mice

Li, Xiaoyan; Guo, Xiamei; Liu, Huicheng; Gao, Guoquan; Xu, Guangqiong; Fei, Xibin; Fang, Xiang; Qiao, Wei; Deng, Guo-Min

doi:10.1016/j.clim.2017.03.015

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…Autoantibodies are involved in the pathogenesis of autoimmune diseases (17). Previous studies showed that lupus patient serum induces tissue damage (18)(19)(20). Serum IgG from lupus patients activates inflammatory cells, such as monocytes/macrophages, dendritic cells and neutrophils, which produce cytokines and subsequently induce tissue damage (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

et al. 2020

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Systemic lupus erythematosus (SLE) is characterized by high levels of autoantibodies and multiorgan tissue damage. The pathogenesis of splenomegaly in SLE remains unknown. In this study, the role of immunoglobulin G (IgG) generation and deposition in the inflammation of the spleen and associated dysfunction in SLE was investigated. In the lupus mice, we observed the development of spontaneous splenomegaly, and we found that lupus serum IgG is an important pathological factor involved in the initiation of inflammation and further germinal center (GC) and plasma cell formation. We discovered that macrophages of the splenic marginal zone are dispensable for the GC response induced by lupus IgG, but red pulp macrophages are important for GC responses. Furthermore, we found that pathogenic lupus IgG promotes inflammation and GC formation through the macrophage-mediated secretion of TNF-α. Syk inhibitor treatment suppressed the changes in the histopathology of the spleen induced by lupus IgG. This study will contribute to the understanding of the pathogenesis of splenomegaly in lupus and promote the development of an effective therapeutic strategy for SLE.

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Section: Introductionmentioning

confidence: 99%

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

et al. 2020

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“…We investigated whether or not serum containing a high level of IgG induces tissue inflammation in order to determine the role of tissue-deposited IgG in the multi-organ and tissue damage that occurs in SLE. Through intra-organ injection of serum from lupus mice and SLE patients (lupus serum), we have established an animal model of SLE organ and tissue damage ( 17 , 20 – 22 , 24 , 27 , 28 ). We found that intra-organ injection of serum from SLE patients and lupus mice, but not from healthy humans and mice, induced tissue inflammation in the skin, liver, spleen, and joints, and that the severity of the inflammation was dose-dependent ( 17 , 23 , 27 , 28 ).…”

Section: Serum-induced Inflammation In Organs and Tissuementioning

confidence: 99%

“…SLE is characterized by a high level of autoantibodies, particularly IgG. Many studies have shown that IgG is involved in the pathogenesis of organ and tissue inflammation and organ damage ( 17 , 20 – 22 , 24 , 27 , 28 , 39 , 40 ). We removed IgG from lupus serum to evaluate the role of IgG in the development of tissue inflammation.…”

Section: Igg Plays a Key Role In Inflammation Induced By Lupus Serummentioning

confidence: 99%

“…Tissue-deposited ICs formed by autoantibodies and autoantigens activate immune cells to produce inflammatory cytokines by binding to Fc gamma receptors (FcgRs) (20-24). Recently, we have demonstrated that organ-deposited IgG induces local inflammation by binding to FcgRs on the surface of monocytes/macrophages, resulting in multi-organ and tissue damage (20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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The role of organ-deposited IgG in the pathogenesis of multi-organ and tissue damage in systemic lupus erythematosus

Qiu

Deng

2022

Front. Immunol.

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Systemic lupus erythematosus (SLE), often known simply as lupus, is a severe chronic autoimmune disease that is characterized by multi-organ and tissue damage and high levels of autoantibodies in serum. We have recently investigated, using animal models, the role of organ-deposited IgG autoantibodies in the pathogenesis of organ and tissue damage in SLE. We found that intra-organ injection of serum from mice with lupus (i.e., lupus mice) into healthy mice triggered inflammation in tissue and organs but that serum from other healthy mice did not, and that the severity of inflammation was related to the dose of serum injected. Immunohistochemistry showed that a large number of IgG molecules are deposited at the site of organ and tissue damage in lupus mice, and that IgG is a major contributor to the development of tissue inflammation triggered by serum from lupus mice or patients. The development of tissue inflammation induced by IgG in serum from lupus mice requires the presence of monocytes/macrophages, but not of lymphocytes or neutrophils; tumor necrosis factor (TNF)/tumor necrosis factor receptor 1 (TNFR1) and interleukin 1 (IL-1) also play essential roles in the development of tissue inflammation triggered by IgG. In addition, it has been found that TNFR1 inhibitors can suppress skin injury in lupus mice and that spleen tyrosine kinase (Syk) inhibitors, which can block the signaling transduction of IgG/Fc gamma receptors (FcγRs), can prevent and treat skin injury and kidney damage in lupus mice. We have also observed that lupus IgG might protect against bone erosion. Based on these results, we conclude that IgG plays a crucial role in the development of organ and tissue damage in SLE and in protecting bone erosion and arthritis, and we suggest that the IgG/FcγR signaling pathway is an important therapeutic target in SLE.

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“…In another LN model based on NZB mice combined with LPS injection, inhibiting ROS and NLRP3 inflammasome pathways also protected kidney functions, by alleviating cell apoptosis and renal histopathology [112]. In a murine lupus model induced by lupus serum, Il-1r -deficient mice and caspase-1 -deficient mice demonstrated major improvements in skin inflammation, with decreased expression of MCP-1 and TNF- α [113], indicating inflammasome pathways contribute to skin inflammation of LN. All these results show that inflammasome-related molecules play roles in lupus progression, including LN.…”

Section: Research In Inflammasome-related Kidney Diseasesmentioning

confidence: 99%

Roles of Inflammasomes in Inflammatory Kidney Diseases

Fan

Xie

Wang

et al. 2019

Mediators of Inflammation

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The immune system has a central role in eliminating detrimental factors, by frequently launching inflammatory responses towards pathogen infection and inner danger signal outbreak. Acute and chronic inflammatory responses are critical determinants for consequences of kidney diseases, in which inflammasomes were inevitably involved. Inflammasomes are closely linked to many kidney diseases such as acute kidney injury and chronic kidney diseases. Inflammasomes are macromolecules consisting of multiple proteins, and their formation initiates the cleavage of procaspase-1, resulting in the activation of gasdermin D as well as the maturation and release of interleukin-1β and IL-18, leading to pyroptosis. Here, we discuss the mechanism in which inflammasomes occur, as well as their roles in inflammatory kidney diseases, in order to shed light for discovering new therapeutical targets for the prevention and treatment of inflammatory kidney diseases and consequent end-stage renal disease.

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Skin inflammation induced by lupus serum was inhibited in IL-1R deficient mice

Cited by 8 publications

References 37 publications

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

Predominant Role of Immunoglobulin G in the Pathogenesis of Splenomegaly in Murine Lupus

The role of organ-deposited IgG in the pathogenesis of multi-organ and tissue damage in systemic lupus erythematosus

Roles of Inflammasomes in Inflammatory Kidney Diseases

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