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https://www.readbyqxmd.com/read/28438897/downregulation-of-mir-200a-3p-targeting-ctbp2-is-involved-in-the-hypoproduction-of-il-2-in-systemic-lupus-erythematosus-derived-t-cells
#1
Eri Katsuyama, Minglu Yan, Katsue Sunahori Watanabe, Syun Matsushima, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Nobuya Yoshida, Vaishali R Moulton, George C Tsokos, Ken-Ei Sada, Jun Wada
Systemic lupus erythematosus (SLE) damages multiple organs by producing various autoantibodies. In this study, we report that decreased microRNA (miR)-200a-3p causes IL-2 hypoproduction through zinc finger E-box binding homeobox (ZEB)1 and C-terminal binding protein 2 (CtBP2) in a lupus-prone mouse. First, we performed RNA sequencing to identify candidate microRNAs and mRNAs involved in the pathogenesis of SLE. We found that miR-200a-3p was significantly downregulated, whereas its putative targets, ZEB2 and CtBP2, were upregulated in CD4(+) T cells from MRL/lpr-Tnfrsf6(lpr) mice compared with C57BL/6J mice...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28430662/histone-demethylase-jmjd3-regulates-cd11a-expression-through-changes-in-histone-h3k27-tri-methylation-levels-in-cd4-t-cells-of-patients-with-systemic-lupus-erythematosus
#2
Heng Yin, Haijing Wu, Ming Zhao, Qing Zhang, Hai Long, Siqi Fu, Qianjin Lu
Aberrant CD11a overexpression in CD4+ T cells induces T cell auto-reactivity, which is an important factor for systemic lupus erythematosus (SLE) pathogenesis. Although many studies have focused on CD11a epigenetic regulation, little is known about histone methylation. JMJD3, as a histone demethylase, is capable of specifically removing the trimethyl group from the H3K27 lysine residue, triggering target gene activation. Here, we examined the expression and function of JMJD3 in CD4+ T cells from SLE patients...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424695/b-cell-tolerance-to-deiminated-histones-in-balb-c-c57bl-6-and-autoimmune-prone-mouse-strains
#3
Nishant Dwivedi, Annica Hedberg, Ying Yi Zheng, Indira Neeli, Minoru Satoh, Laurence Morel, Ole Petter Rekvig, Marko Radic
Deimination, a posttranslational modification of arginine to citrulline carried out by peptidylarginine deiminases, may compromise tolerance of self-antigens. Patients with connective tissue autoimmunity, particularly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or Felty's syndrome, present with autoantibodies to deiminated histones (dH), which thus form a category of antibodies to citrullinated protein antigens (ACPA). In general, ACPA are a sensitive diagnostic for RA and may form in response to the release of nuclear chromatin (DNA plus dH) from granulocytes, usually referred to as neutrophil extracellular traps...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28421864/selfie-autoimmunity
#4
Haseeb Ahsan
The immune system provides protection to tissues damaged by infectious microrganisms or physical damage. In autoimmune diseases, the immune system recognizes and attacks its own tissues i.e., self-destruction. Various agents such as genetic factors and environmental triggers are thought to play a major role in the development of autoimmune diseases. A common feature of all autoimmune diseases is the presence of autoantibodies and inflammation, including mononuclear phagocytes, autoreactive T lymphocytes and autoantibody producing B cells (plasma cells)...
April 19, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/28409523/leptin-levels-in-patients-with-systemic-lupus-erythematosus-inversely-correlate-with-regulatory-t-cell-frequency
#5
X Wang, Y Qiao, L Yang, S Song, Y Han, Y Tian, M Ding, H Jin, F Shao, A Liu
Leptin levels X.W., Y.Q. and L.Y. contributed equally to this work. are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28405179/a-review-of-studies-of-the-proteomes-of-circulating-microparticles-key-roles-for-galectin-3-binding-protein-expressing-microparticles-in-vascular-diseases-and-systemic-lupus-erythematosus
#6
REVIEW
Christoffer T Nielsen, Ole Østergaard, Niclas S Rasmussen, Søren Jacobsen, Niels H H Heegaard
Subcellular microvesicles (MVs) have attracted increasing interest during the past decades. While initially considered as inert cellular debris, several important roles for MVs in physiological homeostasis, cancer, cardiovascular, and autoimmune diseases have been uncovered. Although still poorly understood, MVs are involved in trafficking of information from cell-to-cell, and are implicated in the regulation of immunity, thrombosis, and coagulation. Different subtypes of extracellular MVs exist. This review focuses on the cell membrane-derived shedded MVs (ranging in size from 200 to 1000 nm) typically termed microparticles (MPs)...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28400421/kidney-outcomes-and-risk-factors-for-nephritis-flare-de-novo-in-a-multiethnic-cohort-of-pregnant-patients-with-lupus
#7
Jill P Buyon, Mimi Y Kim, Marta M Guerra, Sifan Lu, Emily Reeves, Michelle Petri, Carl A Laskin, Michael D Lockshin, Lisa R Sammaritano, D Ware Branch, T Flint Porter, Allen Sawitzke, Joan T Merrill, Mary D Stephenson, Elisabeth Cohn, Jane E Salmon
BACKGROUND AND OBJECTIVES: Kidney disease is a critical concern in counseling patients with lupus considering pregnancy. This study sought to assess the risk of renal flares during pregnancy in women with previous lupus nephritis in partial or complete remission, particularly in those with antidouble-stranded DNA antibodies and low complement levels, and the risk of new-onset nephritis in patients with stable/mildly active SLE. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assessed active nephritis (renal flares and de novo kidney disease) and associated predictors during pregnancy in patients with lupus with urine protein ≤1000 mg and serum creatinine <1...
April 11, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28400152/anti-cd3-antibody-therapy-attenuates-the-progression-of-hypertension-in-female-mice-with-systemic-lupus-erythematosus
#8
Keisa W Mathis, Erin B Taylor, Michael J Ryan
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with prevalent hypertension that significantly contributes to the mortality in this patient population. Pre-clinical and clinical evidence suggests that anti-CD3 antibody therapy may attenuate the development of autoimmune diseases like SLE. However, it is unclear whether this treatment impacts the development of the prevalent hypertension associated with SLE. The present study was designed to determine whether anti-CD3 antibody treatment attenuates the progression of hypertension in female SLE mice with already established renal disease (albuminuria ≥100mg/dL)...
April 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28396669/basophil-activation-dependent-autoantibody-and-interleukin-17-production-exacerbate-systemic-lupus-erythematosus
#9
Qingjun Pan, Li Gong, Haiyan Xiao, Yongmin Feng, Lu Li, Zhenzhen Deng, Ling Ye, Jian Zheng, Carol A Dickerson, Lin Ye, Ning An, Chen Yang, Hua-Feng Liu
OBJECTIVE: Autoantibody and inflammatory cytokines play crucial roles in the development of systemic lupus erythematosus (SLE); however, the regulation of their production warrants further investigation. This study aimed to investigate the role of basophil activation in the development of SLE based on studies in patients with SLE and spontaneous lupus-prone MRL-lpr/lpr mice. METHODS: The phenotypes of peripheral basophils and the production of autoantibody and interleukin (IL)-17 in patients with SLE were determined by flow cytometry and enzyme-linked immunosorbent assay, and also their correlations were investigated by statistical analysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28387859/altered-expression-of-signalling-lymphocyte-activation-molecule-receptors-in-t-cells-from-lupus-nephritis-patients-a-potential-biomarker-of-disease-activity
#10
Victoria Stratigou, Anne F Doyle, Francesco Carlucci, Lauren Stephens, Valentina Foschi, Marco Castelli, Nicola McKenna, H Terence Cook, Liz Lightstone, Thomas D Cairns, Matthew C Pickering, Marina Botto
Objectives.: The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Methods.: Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission...
April 5, 2017: Rheumatology
https://www.readbyqxmd.com/read/28383107/a-mouse-model-of-systemic-lupus-erythematosus-responds-better-to-soluble-taci-than-to-soluble-baffr-correlating-with-depletion-of-plasma-cells
#11
Philipp Haselmayer, Michele Vigolo, Josquin Nys, Pascal Schneider, Henry Hess
The TNF family cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR-Fc) or BAFF and APRIL (TACI-Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI-Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28360423/immunometabolism-in-systemic-lupus-erythematosus
#12
REVIEW
Laurence Morel
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4(+) T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes...
March 31, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28352315/daphnetin-inhibits-inflammation-in-the-nzb-w-f1-systemic-lupus-erythematosus-murine-model-via-inhibition-of-nf-%C3%AE%C2%BAb-activity
#13
Min Li, Xiaowei Shi, Fangru Chen, Fei Hao
Daphnetin is a compound extracted from Chinese medicinal herbs, which exerts analgesic and anti-inflammatory effects. The present study aimed to investigate the potential therapeutic effect of daphnetin on inflammation in the NZB/W F1 systemic lupus erythematosus (SLE) murine model. Female NZB/WF1 mice (age, 16-18 weeks) were intraperitoneally injected with daphnetin once a day for 12 weeks. It was revealed that daphnetin treatment significantly increased animal survival rates, reduced renal damage and blood urea nitrogen levels, and suppressed serum autoantibody production in the SLE-prone NZB/W F1 mice...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28351959/the-innate-immune-system-in-human-systemic-lupus-erythematosus
#14
REVIEW
Marc Weidenbusch, Onkar P Kulkarni, Hans-Joachim Anders
Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease...
April 25, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28336124/ultraviolet-b-inhibition-of-dnmt1-activity-via-ahr-activation-dependent-sirt1-suppression-in-cd4-t-cells-from-systemic-lupus-erythematosus-patients
#15
Zhouwei Wu, Xingyu Mei, Zuolin Ying, Yue Sun, Jun Song, Weimin Shi
BACKGROUND: Previous studies have reported that ultraviolet B (UVB) inhibits DNA methyltransferase1 (DNMT1) activity in CD4+ T cells from systemic lupus erythematosus (SLE) patients. Silent mating type information regulation 2 homolog 1 (SIRT1) is a type of Class III histone deacetylases (HDACs), and has been reported to play roles in the pathogenesis of different autoimmune diseases and can modulate DNMT1 activity. Moreover, aryl hydrocarbon receptor (AhR) has been reported to link UVB with SLE...
March 10, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28330896/cell-specific-variation-in-e-selectin-ligand-expression-among-human-peripheral-blood-mononuclear-cells-implications-for-immunosurveillance-and-pathobiology
#16
Mariana Silva, Ronald Kam Fai Fung, Conor Brian Donnelly, Paula Alexandra Videira, Robert Sackstein
Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. In this study, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry and Western blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human PBMCs...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28326889/aquaporin-4-autoimmunity-in-patients-with-systemic-lupus-erythematosus-a-predominantly-population-based-study
#17
Nasrin Asgari, Sven Jarius, Helle Laustrup, Hanne Pb Skejoe, Soeren T Lillevang, Brian G Weinshenker, Anne Voss
BACKGROUND: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. OBJECTIVE: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28325905/evidence-for-c1q-mediated-crosslinking-of-cd33-lair-1-inhibitory-immunoreceptors-and-biological-control-of-cd33-lair-1-expression
#18
Myoungsun Son, Betty Diamond, Bruce T Volpe, Cynthia B Aranow, Meggan C Mackay, Frances Santiago-Schwarz
C1q collagen-like region (CLR) engaging and activating the LAIR-1 inhibitory immunoreceptor represents a non-complement mechanism for maintaining immune quiescence. Given the binding promiscuity of C1q's globular region (gC1q), we hypothesized that C1q concurrently associates with distinct inhibitory immunoreceptors to produce C1q-mediated modulatory networking. Like LAIR-1, CD33 inhibitory immunoreceptors are highly expressed on monocytes. Binding CD33 restricts cell activation/differentiation; however, natural ligands for CD33 remain elusive...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320046/increased-insulin-resistance-and-glucagon-levels-in-mild-inactive-systemic-lupus-patients-despite-normal-glucose-tolerance
#19
Cíntia Nh Miyake, Bruno Gualano, Wagner S Dantas, Renato T Pereira, William Neves, Vanessa O Zambelli, Samuel K Shinjo, Rosa M Pereira, Elizabeth R Silva, Ana Lúcia Sá-Pinto, Eduardo Borba, Hamilton Roschel, Eloisa Bonfá, Fabiana B Benatti
OBJECTIVE: To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT). METHODS: In this cross-sectional study, 33 adult females mild/inactive SLE and 16 age- and body mass index (BMI)-matched female healthy controls (CTRL) underwent a MTT and were assessed for insulin sensitivity and beta-cell function. Skeletal muscle protein expressions of total and membrane GLUT-4 were also evaluated (SLE, n=10; CTRL, n=5); muscle biopsies were performed after MTT...
March 20, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28300427/annexin-a1-as-a-target-for-managing-murine-pristane-induced-systemic-lupus-erythematosus
#20
Nikolina Mihaylova, Silviya Bradyanova, Petroslav Chipinski, Melinda Herbáth, Stela Chausheva, Dobroslav Kyurkchiev, József Prechl, Andrey I Tchorbanov
Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy...
March 16, 2017: Autoimmunity
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