A possible role of Fas-ligand-mediated “reverse signaling” in pathogenesis of rheumatoid arthritis and systemic lupus erythematosus

Telegina, Ekaterina S.; Reshetnyak, T.; Moshnikova, Anna; Proussakova, Olga V.; Zhukova, Aleksandra; Кузнецова, А. В.; Иванов, А. А.; Paltsev, Michail; Beletsky, Igor P.

doi:10.1016/j.imlet.2008.10.003

Cited by 14 publications

(16 citation statements)

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“…147 Fas, a death receptor belonging to the tumor necrosis factor receptor superfamily, is defective in ADs and is also linked to cancer susceptibility. 144,148,149 The phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B,PKB)/mammalian Target Of Rapamycin (mTOR) signaling pathway, known to be altered in leukemia, 150,151 is also involved in the pathogenesis of some ADs. [152][153][154][155][156] The mitogen-activated protein kinases (MAPKs) pathway mediates signal transduction in response to various stimuli, including stress and inflammation.…”

Section: Mechanisms Underlying Autoimmune Diseases In Common With Canmentioning

confidence: 99%

Acute myeloid leukemia developing in patients with autoimmune diseases

Ramadan

Fouad

Summa³

et al. 2011

Haematologica

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Section: Mechanisms Underlying Autoimmune Diseases In Common With Canmentioning

confidence: 99%

Acute myeloid leukemia developing in patients with autoimmune diseases

Ramadan

Fouad

Summa³

et al. 2011

Haematologica

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“…Together, these data suggest that high expression of Fas antigen on lymphocytes might lead to rapid cell turnover and to increased exposure of the immune system to autoantigens, thus leading to autoimmune disease 1,4. Additionally, because sFas can suppress Fas-mediated apoptosis, it has been suggested that sFas can help autoreactive thymocytes to escape negative selection 34. However, the positive correlation between sFas level and dsDNA antibodies suggests a pro-rather than an anti-apoptotic activity of sFas.…”

Section: Introductionmentioning

confidence: 98%

“…This soluble form of Fas causes splenomegaly and lymphadenopathy when injected into normal mice 20,33. Patients with SLE show increased levels of sFas when compared to healthy controls, and a positive correlation was also shown between sFas, leucopenia and anti-dsDNA antibodies 19,33,34. Together, these data suggest that high expression of Fas antigen on lymphocytes might lead to rapid cell turnover and to increased exposure of the immune system to autoantigens, thus leading to autoimmune disease 1,4.…”

Section: Introductionmentioning

confidence: 99%

The Role of Apoptosis Proteins and Complement Components in the Etiopathogenesis of Systemic Lupus Erythematosus

Liphaus

Kiss

2010

Clinics

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Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.

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“…Signaling mediated by the Fas receptor and its natural ligand, FasL, contribute to the pathogenesis of SLE [5–8]. Such signaling contributes to the pathogenesis of various autoimmune diseases by promoting apoptosis and immune escape [9].…”

Section: Introductionmentioning

confidence: 99%

Increased Tim-3 expression on peripheral T lymphocyte subsets and association with higher disease activity in systemic lupus erythematosus

Song

Wang

et al. 2015

Diagn Pathol

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BackgroundBoth the T cell immunoglobulin domain- and mucin domain-containing molecule-3 (Tim-3) and the death receptor Fas contribute to the pathogenesis of various autoimmune diseases, including systemic lupus erythematosus (SLE). The aim of the present study was to determine whether Tim-3 and Fas are co-expressed on certain peripheral T lymphocyte subsets, and whether this expression is associated with greater disease activity in SLE.MethodsPeripheral blood mononuclear cells were isolated from 46 patients newly diagnosed with SLE and 28 age- and sex-matched healthy controls (HCs). Expression of Tim-3 and Fas on T subsets was analyzed by flow cytometry, while mRNA levels of the Tim-3 ligand galectin-9 and Fas ligand FasL were assayed using real-time RT-PCR.ResultsThe proportions of CD3+CD4+ and CD3+CD4- T cells expressing Tim-3+ and Tim+Fas+ were significantly higher in patients than in HCs (p < 0.05), while the proportions of these subtypes expressing Fas were similar for the two groups. Patients with active SLE, as defined by their score on the SLE Disease Activity Index, had lower proportions of CD3+CD4+ T cells and higher proportions of CD3+CD4+Tim-3+ and CD3+CD4+Tim-3+Fas+ T cells than did patients with stable SLE. Serum levels of complement C3 and C4 proteins, considered as a marker of SLE activity, correlated negatively with proportions of CD3+CD4+ and CD3+CD4- T cells expressing Tim-3.ConclusionsExpression of Tim-3 and co-expression of Tim-3 and Fas on certain peripheral T subsets are associated with disease activity in SLE patients. Future research should examine whether the same is true of other T subsets implicated in SLE, and should explore the potential role(s) of Tim-3 in the disease pathway.Virtual slideshttp://www.diagnosticpathology.diagnomx.eu/vs/1855527845145188

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A possible role of Fas-ligand-mediated “reverse signaling” in pathogenesis of rheumatoid arthritis and systemic lupus erythematosus

Cited by 14 publications

References 42 publications

Acute myeloid leukemia developing in patients with autoimmune diseases

Acute myeloid leukemia developing in patients with autoimmune diseases

The Role of Apoptosis Proteins and Complement Components in the Etiopathogenesis of Systemic Lupus Erythematosus

Increased Tim-3 expression on peripheral T lymphocyte subsets and association with higher disease activity in systemic lupus erythematosus

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