<i>DUSP23</i> is over-expressed and linked to the expression of <i>DNMTs</i> in CD4+ T cells from systemic lupus erythematosus patients

Balada, Eva; Felip, Lledó; Ordi‐Ros, Josep; Vilardell‐Tarrés, Miquel

doi:10.1111/cei.12883

Cited by 12 publications

(9 citation statements)

References 46 publications

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“…Thus, it seems that this protein is relevant in controlling T cell responses in order to prevent autoimmune diseases. Interestingly, overexpression of DUSP23 in CD4 T cells of patients with systemic lupus erythematosus has been described [46]. The upregulation of DUSP22 and DUSP23 found in our work by Th1-polarising conditions suggests a regulatory role of these enzymes during T helper polarisation and, consequently, their contribution to the control or development of pathological polarisation should be investigated.…”

Section: Conclusion: Perspective On Autoimmune Diseasessupporting

confidence: 49%

Gene Expression Profiles of Human Phosphotyrosine Phosphatases Consequent to Th1 Polarisation and Effector Function

Castro-Sánchez¹,

Ramirez-Munoz²,

Roda-Navarro³

2017

Journal of Immunology Research

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Phosphotyrosine phosphatases (PTPs) constitute a complex family of enzymes that control the balance of intracellular phosphorylation levels to allow cell responses while avoiding the development of diseases. Despite the relevance of CD4 T cell polarisation and effector function in human autoimmune diseases, the expression profile of PTPs during T helper polarisation and restimulation at inflammatory sites has not been assessed. Here, a systematic analysis of the expression profile of PTPs has been carried out during Th1-polarising conditions and upon PKC activation and intracellular raise of Ca2+ in effector cells. Changes in gene expression levels suggest a previously nonnoted regulatory role of several PTPs in Th1 polarisation and effector function. A substantial change in the spatial compartmentalisation of ERK during T cell responses is proposed based on changes in the dose of cytoplasmic and nuclear MAPK phosphatases. Our study also suggests a regulatory role of autoimmune-related PTPs in controlling T helper polarisation in humans. We expect that those PTPs that regulate T helper polarisation will constitute potential targets for intervening CD4 T cell immune responses in order to generate new therapies for the treatment of autoimmune diseases.

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Section: Conclusion: Perspective On Autoimmune Diseasessupporting

confidence: 49%

Gene Expression Profiles of Human Phosphotyrosine Phosphatases Consequent to Th1 Polarisation and Effector Function

Castro-Sánchez¹,

Ramirez-Munoz²,

Roda-Navarro³

2017

Journal of Immunology Research

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“…Several studies reported that DUSPs also regulate immune-cell responses [23,73,74,75,76]. DUSP2, DUSP4, DUSP7, DUSP10, DUSP12, DUSP22, and DUSP23 are involved in human autoimmune diseases, including SLE [77,78,79,80,81] (Figure 3).…”

Section: Dusp Family Phosphatases Are Involved In T-cell Activatiomentioning

confidence: 99%

MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus

Chuang

Tan

2019

Cells

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T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), which is a severe autoimmune disease. In the past 60 years, only one new therapeutic agent with limited efficacy has been approved for SLE treatment; therefore, the development of early diagnostic biomarkers and therapeutic targets for SLE is desirable. Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) and dual-specificity phosphatases (DUSPs) are regulators of MAP kinases. Several MAP4Ks and DUSPs are involved in T-cell signaling and autoimmune responses. HPK1 (MAP4K1), DUSP22 (JKAP), and DUSP14 are negative regulators of T-cell activation. Consistently, HPK1 and DUSP22 are downregulated in the T cells of human SLE patients. In contrast, MAP4K3 (GLK) is a positive regulator of T-cell signaling and T-cell-mediated immune responses. MAP4K3 overexpression-induced RORγt–AhR complex specifically controls interleukin 17A (IL-17A) production in T cells, leading to autoimmune responses. Consistently, MAP4K3 and the RORγt–AhR complex are overexpressed in the T cells of human SLE patients, as are DUSP4 and DUSP23. In addition, DUSPs are also involved in either human autoimmune diseases (DUSP2, DUSP7, DUSP10, and DUSP12) or T-cell activation (DUSP1, DUSP5, and DUSP14). In this review, we summarize the MAP4Ks and DUSPs that are potential biomarkers and/or therapeutic targets for SLE.

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“…Dual-specificity protein phosphatase 23 (DUSP23) activates the IFN and IL pathways via dephosphorylation (17), and these pathways are responsible for the formation of NETs, which are sources of cfDNA (17, 18, 57). DUSP3, DUSP22, and VH1 participate in both the IL and IFN signaling pathways mainly by dephosphorylating signal transducer and activator of transcription (STAT) proteins (37, 38).…”

Section: Discussionmentioning

confidence: 99%

“…High IFN-α activity is frequently detected in sera from SLE patients (39). Moreover, patients with SLE exhibit a particular mRNA expression profile of IFN-dependent genes in leucocytes known as the IFN signature (17, 40, 41).…”

Section: Discussionmentioning

confidence: 99%

Systemic Lupus Erythematosus and DNA Degradation and Elimination Defects

Arneth

2019

Front. Immunol.

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Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by the production of autoantibodies specific for components of the cell nucleus and that causes damage to body tissues and organs. The pathogenesis of SLE remains unclear, with numerous studies pointing to a combination of genetic and environmental factors. A critical stage in SLE development is cell necrosis, in which undegraded chromatin and nucleoproteins are released into the blood, resulting in circulating cell-free DNA and serum nucleoproteins that trigger anti-dsDNA autoantibody production. This systematic literature review aimed to examine whether SLE stems from a DNA degradation and elimination defect. Materials and Methods: An advanced literature search was conducted in PubMed using the following keywords: [(“SLE” OR “Systemic Lupus Erythematosus” OR “Lupus”)] AND [(“DNA” OR “DNA Degradation”)] AND [(“Defect Elimination”)]. More articles were obtained from the references of the identified articles and basic Google searches. Twenty-five peer-reviewed articles published within the past 10 years (2007–2018) were included for review. Results: The findings of each study are summarized in Tables 1 , 2 . Discussion and Conclusion: The etiopathogenesis of SLE remains controversial, which limits therapeutic inventions for this disease. However, SLE is a DNA degradation and elimination disorder caused by uncleared histones and nuclear material that leak into the extracellular space and form cell-free DNA, triggering an immune response that destroys tissues and organs. Under normal conditions, apoptosis allows DNA and other nuclear material to be efficiently cleared through degradation and additional complex mechanisms such that this material does not trigger the immune system to produce nuclear autoantibodies.

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DUSP23 is over-expressed and linked to the expression of DNMTs in CD4+ T cells from systemic lupus erythematosus patients

Cited by 12 publications

References 46 publications

Gene Expression Profiles of Human Phosphotyrosine Phosphatases Consequent to Th1 Polarisation and Effector Function

Gene Expression Profiles of Human Phosphotyrosine Phosphatases Consequent to Th1 Polarisation and Effector Function

MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus

Systemic Lupus Erythematosus and DNA Degradation and Elimination Defects

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