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SLE AND T cells

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https://www.readbyqxmd.com/read/28500565/dysregulated-lymphoid-cell-populations-in-mouse-models-of-systemic-lupus-erythematosus
#1
REVIEW
Aurélie De Groof, Patrice Hémon, Olivier Mignen, Jacques-Olivier Pers, Edward K Wakeland, Yves Renaudineau, Bernard R Lauwerys
Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic mice), and how they integrate in our present understanding of the pathogenesis of the disease. In particular, we focus on (autoreactive) T cell activation patterns in lupus-prone mice...
May 13, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28479366/cholesterol-accumulation-in-dendritic-cells-links-the-inflammasome-to-acquired-immunity
#2
Marit Westerterp, Emmanuel L Gautier, Anjali Ganda, Matthew M Molusky, Wei Wang, Panagiotis Fotakis, Nan Wang, Gwendalyn J Randolph, Vivette D D'Agati, Laurent Yvan-Charvet, Alan R Tall
Autoimmune diseases such as systemic lupus erythematosus (SLE) are associated with increased cardiovascular disease and reduced plasma high-density lipoprotein (HDL) levels. HDL mediates cholesterol efflux from immune cells via the ATP binding cassette transporters A1 and G1 (ABCA1/G1). The significance of impaired cholesterol efflux pathways in autoimmunity is unknown. We observed that Abca1/g1-deficient mice develop enlarged lymph nodes (LNs) and glomerulonephritis suggestive of SLE. This lupus-like phenotype was recapitulated in mice with knockouts of Abca1/g1 in dendritic cells (DCs), but not in macrophages or T cells...
May 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28471497/haploinsufficiency-of-nadph-oxidase-subunit-ncf2-is-sufficient-to-accelerate-full-blown-lupus-in-nzm-2328-mice
#3
Chaim O Jacob, Ning Yu, Dae-Goon Yoo, Lizet J Perez-Zapata, Emilia Alina Barbu, Mariana J Kaplan, Monica Purmalek, Jeanette T Pingel, Rachel A Idol, Mary C Dinauer
OBJECTIVE: We have previously established that NCF2 (Neutrophil cytosolic factor 2) is a lupus predisposing gene and identified lupus patients with point mutations that are predicted to cause reduced NADPH oxidase activity. This study was undertaken to investigate the relationship between reduced leukocyte NADPH oxidase activity and immune dysregulation associated with SLE. METHODS: We generated NCF2-null mice, in which NADPH oxidase activity is absent, on the non-autoimmune C57BL/6 background and on the NZM...
May 4, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28464513/phagocyte-activity-in-the-peripheral-blood-of-pregnant-women-with-systemic-lupus-erythematosus-and-in-the-cord-blood-of-their-newborns
#4
Gennady T Sukhikh, Valentina G Safronova, Ludmila V Vanko, Nataliya K Matveeva, Anastasiya S Belyaeva, Ekaterina V Fedorova, Marina A Nikolaeva, Nataliya I Klimenchenko, Lyubov V Krechetova
AIM: To detect faults in phagocytosis in peripheral blood cells of pregnant women with systemic lupus erythematosus (SLE) and in cord blood of their newborns. METHODS: Pregnant women fulfilled ≥ 4 American College of Rheumatology criteria for SLE and their newborns were recruited. Pregnant women without SLE and their newborns constituted controls. Phagocytosis and respiratory burst were measured using PHAGOTEST and BURSTTEST kits (Biotechnology GmbH, Germany) on FACSCalibur™ flow cytometer...
May 2, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28455530/nkg2d-cd4-t-cells-kill-regulatory-t-cells-in-a-nkg2d-nkg2d-ligand-dependent-manner-in-systemic-lupus-erythematosus
#5
Di Yang, Zhiqiang Tian, Mengjie Zhang, Weibing Yang, Jun Tang, Yuzhang Wu, Bing Ni
Systemic lupus erythematosus (SLE) features a decreased pool of CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells. We had previously observed NKG2D(+)CD4(+) T cell expansion in contrast to a decreased pool of Treg cells in SLE patients, but whether NKG2D(+)CD4(+) T cells contribute to the decreased Treg cells remains unclear. In the present study, we found that the NKG2D(+)CD4(+) T cells efficiently killed NKG2D ligand (NKG2DL)(+) Treg cells in vitro, whereby the surviving Treg cells in SLE patients showed no detectable expression of NKG2DLs...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28444759/dysregulated-cd46-shedding-interferes-with-th1-contraction-in-systemic-lupus-erythematosus
#6
Ursula Ellinghaus, Andrea Cortini, Christopher L Pinder, Gaelle Le Friec, Claudia Kemper, Timothy J Vyse
IFN-γ-producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: Activation of the complement regulator CD46 and the C3aR expressed by CD4(+) T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN-γ production. Further, CD46-mediated signals also induce co-expression of immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and contracting phase...
April 26, 2017: European Journal of Immunology
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
#7
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
#8
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
#9
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-boon-or-bane
#10
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
#11
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
#12
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
#13
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
#14
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)...
June 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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-)
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