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SLE AND T cells

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https://www.readbyqxmd.com/read/28910360/transgelin-2-is-upregulated-on-activated-b-cells-and-expressed-in-hyperplastic-follicles-in-lupus-erythematosus-patients
#1
Kaori Kiso, Hajime Yoshifuji, Takuma Oku, Masaki Hikida, Koji Kitagori, Yoshitaka Hirayama, Toshiki Nakajima, Hironori Haga, Tatsuaki Tsuruyama, Aya Miyagawa-Hayashino
Transgelin-2 (TAGLN2) is an actin-binding protein that controls actin stability and promotes T cell activation. TAGLN2 is also expressed on B-cells but its function in B-cells is unknown. We found that TAGLN2-expressing B-cells were localized in the germinal center (GC) of secondary lymphoid tissues and TAGLN2 mRNA was significantly upregulated after IgM+IgG stimulation in primary human B-cells, suggesting that TAGLN2 was upregulated upon B-cell activation. In support of this, lymph nodes (LNs) from patients with systemic lupus erythematosus (SLE), in which the intense GC activity have been recognized, showed increased TAGLN2 expression in B-cells compared to control LNs...
2017: PloS One
https://www.readbyqxmd.com/read/28901888/effects-of-oral-lactobacillus-administration-on-antioxidant-activities-and-cd4-cd25-forkhead-box-p3-foxp3-t-cells-in-nzb-w-f1-mice
#2
Bor-Show Tzang, Chung-Hsien Liu, Kuo-Ching Hsu, Yi-Hsing Chen, Chih-Yang Huang, Tsai-Ching Hsu
Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by a dysregulation of the immune system, which causes inflammation responses, excessive oxidative stress and a reduction in the number of cluster of differentiation (CD)4+CD25+forkhead box P3 (FoxP3)+ T cells. Supplementation with certain Lactobacillus strains has been suggested to be beneficial in the comprehensive treatment of SLE. However, little is known about the effect and mechanism of certain Lactobacillus strains on SLE...
September 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28899868/b-cell-derived-il-6-initiates-spontaneous-germinal-center-formation-during-systemic-autoimmunity
#3
Tanvi Arkatkar, Samuel W Du, Holly M Jacobs, Elizabeth M Dam, Baidong Hou, Jane H Buckner, David J Rawlings, Shaun W Jackson
Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell-derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed...
September 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28885337/b-cell-lymphocyte-kinase-polymorphisms-rs13277113-rs2736340-and-rs4840568-and-risk-of-autoimmune-diseases-a-meta-analysis
#4
Chang Zeng, Cheng Fang, Hong Weng, Xiaoqing Xu, Tianyang Wu, Wenhua Li
BACKGROUND: B-cell lymphocyte kinase (BLK) is an inhibitor of B cells that has an important influence on several autoimmune diseases, but there is a lack of comprehensive analysis of its association with autoimmune diseases. Hence, it is meaningful to conduct a comprehensive analysis. METHODS: A systematic literature search was performed on the PubMed, ScienceDirect, and Web of Science databases up to June 30, 2016. The data were extracted and quality-assessed before conducting the meta-analysis...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28877244/the-role-of-dietary-sodium-intake-on-the-modulation-of-t-helper-17-cells-and-regulatory-t-cells-in-patients-with-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#5
Rossana Scrivo, Laura Massaro, Cristiana Barbati, Marta Vomero, Fulvia Ceccarelli, Francesca Romana Spinelli, Valeria Riccieri, Alessandra Spagnoli, Cristiano Alessandri, Giovambattista Desideri, Fabrizio Conti, Guido Valesini
We aimed at investigating whether the frequency and function of T helper 17 (Th17) and regulatory T cells (Treg) are affected by a restriction of dietary sodium intake in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We enrolled RA and SLE patients not receiving drugs known to increase urinary sodium excretion. Patients underwent a dietary regimen starting with a restricted daily sodium intake followed by a normal-sodium daily intake. The timepoints were identified at baseline (T0), after 3 weeks of low-sodium dietary regimen (T3), after 2 weeks of normal-sodium dietary regimen (T5)...
2017: PloS One
https://www.readbyqxmd.com/read/28876451/selective-hdac6-inhibition-decreases-early-stage-of-lupus-nephritis-by-downregulating-both-innate-and-adaptive-immune-responses
#6
Jingjing Ren, Xiaofeng Liao, Miranda D Vieson, Miao Chen, Reilly Scott, Jillian Kazmierczak, Xin M Luo, Christopher M Reilly
We have previously demonstrated that HDAC6 expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) NZB/W F1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for five weeks...
September 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28859258/lupus-associated-functional-polymorphism-in-pnp-causes-cell-cycle-abnormalities-and-interferon-pathway-activation-in-human-immune-cells
#7
Yogita Ghodke-Puranik, Jessica M Dorschner, Danielle M Vsetecka, Shreyasee Amin, Ashima Makol, Floranne Ernste, Thomas Osborn, Kevin Moder, Vaidehi Chowdhary, Elias Eliopoulos, Maria I Zervou, George N Goulielmos, Mark A Jensen, Timothy B Niewold
BACKGROUND: Systemic lupus erythematosus (SLE) is frequently characterized by type I interferon (IFN) pathway activation. We previously found a missense SNP in the purine nucleoside phosphorylase (PNP) gene was associated with high IFN in SLE (rs1049564, P=1.24 x10(-7) ). PNP is a key enzyme in purine metabolism. In this study, we perform functional follow-up of this polymorphism in human cells. METHODS: Type I IFN was measured in patient sera using a reporter cell assay...
August 31, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28853005/unmet-needs-in-the-pathogenesis-and-treatment-of-systemic-lupus-erythematosus
#8
REVIEW
Jyoti Bakshi, Beatriz Tejera Segura, Christopher Wincup, Anisur Rahman
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a prevalence of approximately 1 in 1000. Over the last 30 years, advances in treatment such as use of corticosteroids and immunosuppressants have improved life expectancy and quality of life for patients with lupus and the key unmet needs have therefore changed. With the reduced mortality from disease activity, development of cardiovascular disease (CVD) has become an increasingly important cause of death in patients with SLE. The increased CVD risk in these patients is partly, but not fully explained by standard risk factors, and abnormalities in the immune response to lipids may play a role...
August 29, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28844943/the-unknown-aspect-of-baff-inducing-il-35-production-by-a-cd5-cd1d-hi-fc%C3%AE-riib-hi-regulatory-b-cell-subset-in-lupus
#9
Yamin Zhang, Jun Li, Nuoya Zhou, Yi Zhang, Min Wu, Jian Xu, Chen Shen, Xiangjie An, Guanxin Shen, Ming Yang, Chun Zhang, Juan Tao
IL-35 is a critical immunosuppressive cytokine and plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in SLE, also a dichotomous regulator for B cell immune responses, has an effect on IL-35-producing regulatory B cells and its underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Fas(lpr/lpr) mice. BAFF-induced IL-35-producing B cells were mainly from MZ B cell subset and exhibited a CD5(+)CD1d(hi)FcγRIIb(hi) phenotype...
August 24, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28837808/elevated-expression-of-microrna-873-facilitates-th17-differentiation-by-targeting-forkhead-box-o1-foxo1-in-the-pathogenesis-of-systemic-lupus-erythematosus
#10
Lining Liu, Yifan Liu, Min Yuan, Liming Xu, Huanxia Sun
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated that miR-873 expression was significantly up-regulated in patients with SLE, and its expression was positively associated with the disease severity. CD4(+) T cells, especially the Th17 subset, were found to be the major source of miR-873 expression. Using gain- and loss-of-function approaches, we further showed that miR-873 could facilitate the differentiation of CD4(+) T cells into Th17 lineage...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28830352/jak-inhibitor-has-the-amelioration-effect-in-lupus-prone-mice-the-involvement-of-ifn-signature-gene-downregulation
#11
Keigo Ikeda, Kunihiro Hayakawa, Maki Fujishiro, Mikiko Kawasaki, Takuya Hirai, Hiroshi Tsushima, Tomoko Miyashita, Satoshi Suzuki, Shinji Morimoto, Naoto Tamura, Kenji Takamori, Hideoki Ogawa, Iwao Sekigawa
BACKGROUND: We previously reported that JAK-STAT-pathway mediated regulation of IFN-regulatory factor genes could play an important role in SLE pathogenesis. Here, we evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK-STAT pathway and as a therapeutic for SLE. RESULTS: We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4(+) T cells (SLE mice) and CD3(+) T cells (human SLE patients) were measured by DNA microarray and qRT-PCR...
August 22, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28829572/immunomodulatory-therapy-of-inflammatory-liver-disease-using-selectin-binding-glycopolymers
#12
Matthias Bartneck, Christopher Thorsten Schlößer, Matthias Barz, Rudolf Zentel, Christian Trautwein, Twan Lammers, Frank Tacke
Immunotherapies have the potential to significantly advance treatment of inflammatory disease and cancer, which are in large parts driven by immune cells. Selectins control the first step in immune cell adhesion and extravasation, thereby guiding leukocyte trafficking to tissue lesions. We analyzed four different highly specific selectin-binding glycopolymers, based on linear poly(2-hydroxypropyl)-methacrylamide (PHPMA) polymers. These glycopolymers contain either the tetrasaccharide sialyl-Lewis(X) (SLe(X)), or the individual carbohydrates fucose, galactose, and sialic acids mimicking the complex SLe(X) binding motive...
August 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28821990/upregulation-of-cd16-monocyte-subsets-in-systemic-lupus-erythematous-patients
#13
Ziyan Wu, Shulan Zhang, Lidan Zhao, Yunyun Fei, Li Wang, Jing Li, Xiaoting Wen, Xiaofeng Zeng, Fengchun Zhang, Yongzhe Li
Monocytes are an important component in the innate immune system. However, studies to date have failed to conclude whether their levels are altered in patients with systemic lupus erythematosus (SLE). We applied the cytodiff counting method and comprehensively measured the circulating levels of distinct white blood cell (WBC) subsets, including CD16+, CD16-, and total monocytes, in 61 SLE patients as well as in 203 age-matched healthy controls (HCs). The absolute number of CD16- monocytes, total monocytes, immature granulocytes, mature neutrophils, total neutrophils, and T cell blasts was significantly higher, that of non-cytotoxic T lymphocytes, cytotoxic T + NK lymphocytes, T + NK lymphocytes, total lymphocytes, basophils, and eosinophils significantly lower (all p < 0...
August 19, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28820360/preliminary-study-on-the-changes-of-ovarian-reserve-menstruation-and-lymphocyte-subpopulation-in-systemic-lupus-erythematosus-sle-patients-of-childbearing-age
#14
H Gao, J Ma, X Wang, T Lv, J Liu, Y Ren, Y Li, Y Zhang
Objective The main aim of this study was to investigate the ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age. Methods We enrolled 40 SLE patients of childbearing age and 40 age-matched healthy controls. Anti-Müllerian hormone (AMH) was tested by electrochemiluminescence, and lymphocyte subsets were tested by flow cytometry. Menstruation situation was obtained by interview. Results The AMH level of the SLE group was significantly lower than that of the control group ( p < 0...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28818832/b-cell-ox40l-supports-t-follicular-helper-cell-development-and-contributes-to-sle-pathogenesis
#15
Andrea Cortini, Ursula Ellinghaus, Talat H Malik, Deborah S Cunninghame Graham, Marina Botto, Timothy James Vyse
OBJECTIVES: TNFSF4 (encodes OX40L) is a susceptibility locus for systemic lupus erythematosus (SLE). Risk alleles increase TNFSF4 expression in cell lines, but the mechanism linking this effect to disease is unclear, and the OX40L-expressing cell types mediating the risk are not clearly established. Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus. METHODS: We used a conditional knockout mouse system to investigate the function of OX40L on B and T lymphocytes in systemic autoimmunity...
August 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28818099/biosemantics-guided-gene-expression-profiling-of-sj%C3%A3-gren-s-syndrome-a-comparative-analysis-with-systemic-lupus-erythematosus-and-rheumatoid-arthritis
#16
Nirav R Shah, Braxton D Noll, Craig B Stevens, Michael T Brennan, Farah B Mougeot, Jean-Luc C Mougeot
BACKGROUND: Sjögren's syndrome (SS) shares many clinical and pathological similarities with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These autoimmune diseases mostly affect women. In this study, concept profile analysis (CPA) and gene expression meta-analysis were used to identify genes potentially involved in SS pathogenesis. METHODS: Human genes associated with SS, SLE, and RA were identified using the CPA tool, Anni 2.1. The differential mRNA expression of genes common to SS and SLE (SS-SLE) was determined in female peripheral blood mononuclear cells (PBMCs) using NCBI-GEO2R...
August 17, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28811467/the-mtorc1-4e-bp-eif4e-axis-controls-de-novo-bcl6-protein-synthesis-in-t-cells-and-systemic-autoimmunity
#17
Woelsung Yi, Sanjay Gupta, Edd Ricker, Michela Manni, Rolf Jessberger, Yurii Chinenov, Henrik Molina, Alessandra B Pernis
Post-transcriptional modifications can control protein abundance, but the extent to which these alterations contribute to the expression of T helper (TH) lineage-defining factors is unknown. Tight regulation of Bcl6 expression, an essential transcription factor for T follicular helper (TFH) cells, is critical as aberrant TFH cell expansion is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we show that lack of the SLE risk variant Def6 results in deregulation of Bcl6 protein synthesis in T cells as a result of enhanced activation of the mTORC1-4E-BP-eIF4E axis, secondary to aberrant assembly of a raptor-p62-TRAF6 complex...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28805301/the-lymphocytes-stimulation-induced-dna-release-a-phenomenon-similar-to-netosis
#18
Yermis Carolina Rocha, Mauricio Rojas, Gloria Vásquez, Juan López
The release of DNA into the extracellular milieu by neutrophil during a process called NETosis has been postulated as an additional source of autoantigens; a process believed to be important in the pathogenesis of some autoimmune disease, such as Systemic Lupus Erythematosus (SLE). However, it is not established if the B and T cells undergo the release of DNA to the extracellular milleu, in response to different stimuli. In this study, it was observed that, the treatment of B and T cells with PMA, ionomycin, and the serum from patients with SLE induced the extracellular DNA presence in B and T cells...
August 11, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28801578/basophils-contribute-to-pristane-induced-lupus-like-nephritis-model
#19
Barbara Dema, Yasmine Lamri, Christophe Pellefigues, Emeline Pacreau, Fanny Saidoune, Caroline Bidault, Hajime Karasuyama, Karim Sacré, Eric Daugas, Nicolas Charles
Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure. Autoantibodies to nuclear antigens and autoreactive B and T cells are central in SLE pathogenesis. Immune mechanisms amplifying this autoantibody production drive flares of the disease. We previously showed that basophils were contributing to LN development in a spontaneous lupus-like mouse model (constitutive Lyn (-/-) mice) and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793932/hydroxychloroquine-inhibits-cd154-expression-in-cd4-t-lymphocytes-of-systemic-lupus-erythematosus-through-nfat-but-not-stat5-signaling
#20
Shu-Fen Wu, Chia-Bin Chang, Jui-Mei Hsu, Ming-Chi Lu, Ning-Sheng Lai, Chin Li, Chien-Hsueh Tung
BACKGROUND: Overexpression of membranous CD154 in T lymphocytes has been found previously in systemic lupus erythematosus (SLE). Because hydroxychloroquine (HCQ) has been used frequently in the treatment of lupus, we sought to identify the effects of HCQ on CD154 and a possibly regulatory mechanism. METHODS: CD4(+) T cells were isolated from the blood of lupus patients. After stimulation with ionomycin or IL-15 and various concentrations of HCQ, expression of membranous CD154 and NFAT and STAT5 signaling were assessed...
August 9, 2017: Arthritis Research & Therapy
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