Cell Membrane-bound TLR2 and TLR4: Potential Predictors of Active Systemic Lupus Erythematosus and Lupus Nephritis

Pérez-Ferro, María; Castillo, Cristina Serrano del; Sánchez‐Pernaute, Olga

doi:10.3899/jrheum.151386

Cited by 20 publications

(15 citation statements)

References 11 publications

(11 reference statements)

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“…TLRs have been widely implicated as the pathogenic drivers in SLE, and TLR2, TLR4, TLR7, and TLR9 have been shown to be expressed at higher levels in B cells, peripheral blood mononuclear cells (PBMC), or kidney tissues [19–22]. Moreover, LXR agonists have been shown to regulate TLR-induced macrophage cytokine secretion with TLR agonists [23–26].…”

Section: Resultsmentioning

confidence: 99%

The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRα Polymorphism

Kim

Han

Jung

et al. 2019

Mediators of Inflammation

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Liver X receptors (LXRs) have emerged as important regulators of inflammatory gene expression. Previously, we had reported that an LXRα gene promoter polymorphism (-1830 T > C) is associated with systemic lupus erythematosus (SLE). Therefore, we assessed cytokine expression in relation to LXRα polymorphism in monocyte-derived macrophages from patients with SLE. Macrophages were obtained after 72 hours of culture of human monocytes supplemented with phorbol 12-myristate 13-acetate. Cells were transfected with LXRα promoter constructs. Additionally, peripheral blood mononuclear cell- (PBMC-) derived macrophages from the patients were evaluated for proinflammatory cytokines in relation to the genotypes of LXRα -1830 T > C. The expression of LXRα was increased in macrophages; levels of proinflammatory cytokines were decreased with LXRα expression. Production of proinflammatory cytokines varied depending on LXRα -1830 T > C genotype. In particular, expression of LXRα was decreased and that of proinflammatory cytokines was increased for LXRα -1830 TC genotype compared to that for TT genotype. The data were consistent in PBMC-derived macrophages from patients with SLE. Increased proinflammatory cytokines is related to TLR7 and TLR9 expression. These data suggest that the expression levels of LXRα, according to LXRα -1830 T > C genotype, may contribute to the inflammatory response by induction of inflammatory cytokines in SLE.

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Section: Resultsmentioning

confidence: 99%

The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRα Polymorphism

Kim

Han

Jung

et al. 2019

Mediators of Inflammation

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“…Proteinuria has been associated with TLR2 activation in the kidneys, leading to inflammation in albumin-overloaded nephropathy rats and patients with non-IgA mesangioproliferative glomerulonephritis [27]. In patients with systemic lupus erythematosus and concurrent active nephritis, the level of TLR2 in peripheral blood T cells and of TLR4 in B cells and monocytes was increased, and the rate of protein excretion in the urine was associated with TLR expression in these cells [15].…”

Section: Discussionmentioning

confidence: 99%

“…Due to its role in the immune response, TLR signaling may play a part in autoimmune disorders affecting the kidneys. TLRs have been implicated in systemic lupus erythematosus [15,16] and immunoglobulin (Ig) A nephropathy [17]. Furthermore, many of the kidney diseases are the consequences of various infections.…”

Section: Introductionmentioning

confidence: 99%

TLR2 Expression on Select Lymphocyte Subsets as a New Marker in Glomerulonephritis

Mertowski

Grywalska

Gosik

et al. 2020

JCM

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Toll-like receptor (TLR) signaling may be involved in autoimmune kidney disorders and has been implicated in proliferative and non-proliferative glomerulonephritis (PGN and NPGN). In this study, we investigated the expression of TLR2 on T and B lymphocytes in relation to selected clinical parameters in patients with PGN and NPGN. We collected peripheral blood from the ulnar vein of patients with PGN (n = 15) or NPGN (n = 22) and healthy volunteers (n = 20). The percentage of peripheral blood mononuclear cells expressing TLR2 was determined with flow cytometry. TLR2 expression on T and B lymphocytes was increased in PGN patients compared with NPGN patients and controls (p ≤ 0.001). In patients with PGN, TLR2 expression correlated negatively with the serum concentrations of IgG and albumin and positively with urine protein excretion. Receiver operating characteristic (ROC) analysis indicated that TLR2 expression is a highly specific marker to distinguish PGN patients from NPGN patients and controls, especially on CD4+ T lymphocytes. Its use as a non-invasive marker of disease should be further investigated.

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“…Toll-like receptor 4 was proposed to play an important role in various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis (19–21). Our previous study also showed increased expression levels of TLR4 and its downstream effectors in the lymph nodes in a PM animal model (24).…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4–Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Inflammatory Development of Polymyositis by Mediating Interferon-γ and Interleukin-17A in Humans and Experimental Autoimmune Myositis Mouse Model

Hong-ya

Shi

et al. 2017

Front. Neurol.

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ObjectiveToll-like receptor 4 (TLR4) is one of the key players in the development of many autoimmune diseases. To determine the possible role of TLR4 in polymyositis (PM) development, we collected muscle samples from PM patients and mice subjected to an experimental autoimmune myositis (EAM) model.MethodsWe measured TLR4–MyD88 pathway-related factors, interferon-γ (IFN-γ), and interleukin-17A (IL-17A) in EAM mice and PM patients. Then, we observed the changes of above factors and the inflammatory development of EAM mice with TLR4 antagonist TAK-242, IFN-γ, or IL-17A antibody treatment.ResultsThe expression of TLR4, MyD88, and NF-κB was significantly upregulated in the muscle tissues both in 22 patients with PM and in the EAM model. As expected, increased levels of various cytokines, such as IL-1β, IL-6, IL-10, IL-12, tumor necrosis factor-α, TGF-β, IFN-γ, and IL-17A, were evident in the serum of EAM mice. Moreover, mRNA expression levels of IFN-γ and IL-17A were significantly increased in both PM patients and EAM mice. Consistently, the levels of these factors were positively correlated with the degree of muscle inflammation in EAM mice. However, when EAM mice were treated with TLR4 antagonist TAK-242, the expression of IFN-γ and IL-17A was decreased. When the cytokines were neutralized by anti-IFN-γ or anti-IL-17A antibody, the inflammatory development of EAM exacerbated or mitigated.ConclusionThe present study provided the important evidence that the TLR4–MyD88 pathway may be involved in the immune mechanisms of PM by mediating IFN-γ and IL-17A.

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Cell Membrane-bound TLR2 and TLR4: Potential Predictors of Active Systemic Lupus Erythematosus and Lupus Nephritis

Cited by 20 publications

References 11 publications

The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRα Polymorphism

The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRα Polymorphism

TLR2 Expression on Select Lymphocyte Subsets as a New Marker in Glomerulonephritis

Toll-Like Receptor 4–Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Inflammatory Development of Polymyositis by Mediating Interferon-γ and Interleukin-17A in Humans and Experimental Autoimmune Myositis Mouse Model

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