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SLE AND T cells

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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
#1
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
#2
Andrea Cortini, Ursula Ellinghaus, Talat H Malik, Deborah S Cunningham Grahman, 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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28783690/cross-talk-between-inkt-cells-and-monocytes-triggers-an-atheroprotective-immune-response-in-sle-patients-with-asymptomatic-plaque
#8
Edward Smith, Sara Croca, Kirsty E Waddington, Reecha Sofat, Maura Griffin, Andrew Nicolaides, David A Isenberg, Ines Pineda Torra, Anisur Rahman, Elizabeth C Jury
Accelerated atherosclerosis is a complication of the autoimmune rheumatic disease systemic lupus erythematosus (SLE). We questioned the role played by invariant natural killer T (iNKT) cells in this process because they not only are defective in autoimmunity but also promote atherosclerosis in response to CD1d-mediated lipid antigen presentation. iNKT cells from SLE patients with asymptomatic plaque (SLE-P) had increased proliferation and interleukin-4 production compared with those from SLE patients with no plaque...
December 2, 2016: Science Immunology
https://www.readbyqxmd.com/read/28780965/regulation-of-systemic-autoimmunity-and-cd11c-tbet-b-cells-by-swef-proteins
#9
Michela Manni, Edd Ricker, Alessandra B Pernis
Recent studies have revealed the existence of a T-bet dependent subset of B cells, which expresses unique phenotypic and functional characteristics including high levels of CD11c and CD11b. In the murine system this B cell subset has been termed Age/autoimmune-associated B cells (ABCs) since it expands with age in non-autoimmune mice and it prematurely accumulates in autoimmune-prone strains. The molecular mechanisms that promote the expansion and function of ABCs are largely unknown. This review will focus on the SWEF proteins, a small family of Rho GEFs comprised of SWAP-70 and its homolog DEF6, a newly identified risk variant for human SLE...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28764616/effector-t-cells-are-expanded-in-systemic-lupus-erythematosus-patients-with-high-disease-activity-and-damage-indexes
#10
S Piantoni, F Regola, A Zanola, L Andreoli, F Dall'Ara, A Tincani, P Airo'
Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28763099/autologous-tolerogenic-dendritic-cells-derived-from-monocytes-of-systemic-lupus-erythematosus-patients-and-healthy-donors-show-a-stable-and-immunosuppressive-phenotype
#11
Javiera Obreque, Fabián Vega, Andy Torres, Loreto Cuitino, Juan P Mackern-Oberti, Paola Viviani, Alexis Kalergis, Carolina Llanos
Systemic Lupus Erythematosus (SLE) is an autoimmune disease with unrestrained T-cell and B cell activity towards self-antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte-derived dendritic cells (DCs) from healthy controls (HC) and SLE patients were treated with dexamethasone (DEXA) and rosiglitazone (RGZ) to induce tolDCs...
August 1, 2017: Immunology
https://www.readbyqxmd.com/read/28756336/tnf%C3%AE-and-il-1%C3%AE-in-the-synovial-fluid-facilitate-mucosal-associated-invariant-t-mait-cell-migration
#12
Miok Kim, Su-Jin Yoo, Seong Wook Kang, Jaeyul Kwon, Inpyo Choi, Chang Hoon Lee
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood. The aim of this study was to determine whether human MAIT cells preferentially traffick to inflamed synovial sites in rheumatoid arthritis patients and to elucidate the underlying mechanism...
July 27, 2017: Cytokine
https://www.readbyqxmd.com/read/28754800/frontline-science-tim-3-mediated-dysfunctional-engulfment-of-apoptotic-cells-in-sle
#13
Di Zhao, Min Guo, Bing Liu, Qinghai Lin, Tingting Xie, Qianqian Zhang, Xiaoxia Jia, Qiang Shu, Xiaohong Liang, Lifen Gao, Chunhong Ma
T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells, which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed the key cytoplasmic domain for signal transduction...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28747257/cells-with-treg-specific-foxp3-demethylation-but-low-cd25-are-prevalent-in-autoimmunity
#14
Ricardo C Ferreira, Henry Z Simons, Whitney S Thompson, Daniel B Rainbow, Xin Yang, Antony J Cutler, Joao Oliveira, Xaquin Castro Dopico, Deborah J Smyth, Natalia Savinykh, Meghavi Mashar, Tim J Vyse, David B Dunger, Helen Baxendale, Anita Chandra, Chris Wallace, John A Todd, Linda S Wicker, Marcin L Pekalski
Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3(+) cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3(+) cells within CD127(low)CD25(low) CD4(+) T cells (here defined as CD25(low)FOXP3(+) T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes...
July 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28745239/therapeutic-interventions-of-tissue-specific-autoimmune-onset-in-systemic-lupus-erythematosus
#15
Subhajit Dasgupta
Systemic lupus erythematosus (SLE) is a female predominant autoimmune disease. The onset of SLE has been found to affect kidney, bone, cardiovascular and central nervous system. Auto activation of B cells and T helper cells together are known to develop self-reactive immune responses in SLE. The therapy still includes corticosteroids to prevent allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit to control disease manifestations...
July 25, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28741259/adoptive-transfer-of-autoimmune-splenic-dendritic-cells-to-lupus-prone-mice-triggers-a-b-lymphocyte-humoral-response
#16
Daniela Sauma, Natalia Crisóstomo, Camila Fuentes, María Alejandra Gleisner, Yessia Hidalgo, María José Fuenzalida, Mario Rosemblatt, María Rosa Bono
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by increased autoantibody production that leads to multiple tissue injuries. Dendritic cells (DCs) are important orchestrators of immune responses and key components in fine-tuning the balance between tolerance and immunity. However, their role in autoimmune disorders such as SLE remains uncertain. We analyzed the contribution of DCs in triggering SLE by adoptively transferring splenic DCs from aged autoimmune [NZB×NZW]F1 (BWF1) mice to young healthy BWF1 mice...
August 2017: Immunologic Research
https://www.readbyqxmd.com/read/28740209/novel-risk-genes-for-systemic-lupus-erythematosus-predicted-by-random-forest-classification
#17
Jonas Carlsson Almlöf, Andrei Alexsson, Juliana Imgenberg-Kreuz, Lina Sylwan, Christofer Bäcklin, Dag Leonard, Gunnel Nordmark, Karolina Tandre, Maija-Leena Eloranta, Leonid Padyukov, Christine Bengtsson, Andreas Jönsen, Solbritt Rantapää Dahlqvist, Christopher Sjöwall, Anders A Bengtsson, Iva Gunnarsson, Elisabet Svenungsson, Lars Rönnblom, Johanna K Sandling, Ann-Christine Syvänen
Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736280/the-serine-threonine-protein-phosphatase-2a-controls-autoimmunity
#18
Amir Sharabi, Isaac R Kasper, George C Tsokos
Protein phosphatase 2A (PP2A) is the first Ser/Thr phosphatase recognized to contribute to human and murine lupus immunopathology. PP2A expression in SLE is controlled both epigenetically and genetically, and it is increased in patients with SLE, which contributes to decreased IL-2 production, decreased CD3ζ and increased FcRγ expression on the surface of T cells, increased CREMα expression, hypomethylation of genes associated with SLE pathogenesis, and increased IL-17 production. B regulatory subunit of PP2A regulates IL-2 deprivation-induced T cell death and is decreased in SLE patients...
July 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28723645/altered-micrornas-expression-in-t-cells-of-patients-with-sle-involved-in-the-lack-of-vitamin-d
#19
Dao-Jun Chen, Lan-Ju Li, Xiao-Ke Yang, Tao Yu, Rui-Xue Leng, Hai-Feng Pan, Dong-Qing Ye
Vitamin D has been recognized as a potent immunomodulator and its deficiency is common in different population groups including patients with SLE. As miRNAs regulation plays a significant role in SLE, the present study aimed to evaluate the association between vitamin D status and miRNAs levels in patients with SLE. The serum concentrations of vitamin D (25-hydroxyvitamin D) and the levels of six miRNAs in T cells from patients with SLE were measured in 42 SLE cases and 48 healthy controls. Vitamin D treatment was also performed in isolated and cultured T cells from SLE patients in different times and doses...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722110/renal-infiltrating-cd11c-cells-are-pathogenic-in-murine-lupus-nephritis-through-promoting-cd4-t-cell-responses
#20
Xiaofeng Liao, Jingjing Ren, Alec Reihl, Tharshikha Pirapakaran, Bharath Sreekumar, Thomas E Cecere, Christopher M Reilly, Xin M Luo
Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE) causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c(+) myeloid cell population in LN...
July 19, 2017: Clinical and Experimental Immunology
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