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https://www.readbyqxmd.com/read/28719617/microrna-155-deficiency-leads-to-decreased-autoantibody-levels-and-reduced-severity-of-nephritis-and-pneumonitis-in-pristane-induced-lupus
#1
Harald Leiss, Wilhelm Salzberger, Barbara Jacobs, Irina Gessl, Nicolas Kozakowski, Stephan Blüml, Antonia Puchner, Attila Kiss, Bruno K Podesser, Josef S Smolen, Georg H Stummvoll
OBJECTIVE: We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus. MATERIALS AND METHODS: Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28718063/new-insights-on-platelets-and-platelet-derived-microparticles-in-systemic-lupus-erythematosus
#2
REVIEW
Marc Scherlinger, Vanja Sisirak, Christophe Richez, Estibaliz Lazaro, Pierre Duffau, Patrick Blanco
PURPOSE OF REVIEW: Current knowledge on the role of platelets and platelet-derived microparticles (PMPs) on the immune system has been fast-growing. Systemic lupus erythematosus (SLE) is a systemic auto-immune disorder characterized by a loss of tolerance toward nuclear auto-antigens. Although recent studies allowed a better understanding of SLE pathogenesis, there is an urgent need for the development of new treatments and the identification of new biomarkers to assess the disease activity...
August 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28709914/the-ratio-of-circulating-follicular-t-helper-cell-to-follicular-t-regulatory-cell-is-correlated-with-disease-activity-in-systemic-lupus-erythematosus
#3
Bihua Xu, Shuang Wang, Mianjing Zhou, Yuefang Huang, Rong Fu, Chaohuan Guo, Jingxian Chen, Jijun Zhao, Felicia Gaskin, Shu Man Fu, Niansheng Yang
Follicular T regulatory (Tfr) cells inhibit follicular T helper (Tfh) cells mediated B cell responses. Tfh cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of Tfr cells in SLE remains unclear. The frequency of circulating Tfr and Tfh cells were examined in SLE patients and healthy controls. The frequency of circulating Tfr cell decreased and Tfh/Tfr ratio increased in SLE patients. Serum anti-dsDNA antibody level positively correlated with frequency of Tfh cells and Tfh/Tfr ratios but negatively correlated with the frequency of Tfr cells...
July 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28692793/rare-x-chromosome-abnormalities-in-systemic-lupus-erythematosus-and-sj%C3%A3-gren-s-syndrome
#4
Rohan Sharma, Valerie M Harris, Joshua Cavett, Biji T Kurien, Ke Liu, Kristi A Koelsch, Anum Fayaaz, Kaustubh S Chaudhari, Lida Radfar, David Lewis, Donald U Stone, C Erick Kaufman, Shibo Li, Barbara Segal, Daniel J Wallace, Michael H Weisman, Swamy Venuturupalli, Jennifer A Kelly, Bernardo Pons-Estel, Roland Jonsson, Xianglan Lu, Jacques-Eric Gottenberg, Juan-Manuel Anaya, Deborah S Cunninghame-Graham, Andrew J W Huang, Michael T Brennan, Pamela Hughes, Ilias Alevizos, Corinne Miceli-Richard, Edward C Keystone, Vivian P Bykerk, Gideon Hirschfield, Gang Xie, Gunnel Nordmark, Sara Magnusson Bucher, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Marie Wahren-Herlenius, Torsten Witte, Marta Alarcon-Riquelme, Xavier Mariette, Christopher J Lessard, John B Harley, Wan-Fai Ng, Astrid Rasmussen, Kathy L Sivils, R Hal Scofield
BACKGROUND: Sjögren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease suggesting a dose effect on the X chromosome. METHODS: We examined cohorts of Sjögren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects...
July 10, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28683581/reduction-of-cd19-autoimmunity-marker-on-b-cells-of-paediatric-sle-patients-through-repressing-pu-1-tnf-%C3%AE-baff-axis-pathway-by-mir-155
#5
H R Aboelenein, M T Hamza, H Marzouk, R A Youness, M Rahmoon, S Salah, A I Abdelaziz
microRNA-155 (miR-155) is implicated in regulating B-cell activation and survival that is important in systemic lupus erythematosus (SLE) pathogenesis. PU.1, a target for miR-155, is a crucial regulator of B-cell development and enhances Tumour-Necrosis-factor-alpha (TNF-α) expression. TNF-α induces the expression of B-cell-activating-factor (BAFF). BAFF is reported to increase the expression of the autoimmunity marker; CD19. This study aimed to investigate the regulation of expression of PU.1 in pediatric-systemic-lupus-erythematosus (pSLE) patients by miR-155, and hence evaluate its impact on TNF-α/BAFF/CD19 signalling pathway...
July 7, 2017: Growth Factors
https://www.readbyqxmd.com/read/28676527/the-id-genotype-of-mdm2-40-bp-insertion-deletion-polymorphism-was-associated-with-lower-risk-of-sle
#6
Saeedeh Salimi, Mahnaz Rezaei, Abbas Mohammadpour-Gharehbagh, Mojtaba Sajadian, Mahnaz Sandoughi
BACKGROUND: In patients with systemic lupus erythematosus (SLE), loss of immunological tolerance to self-nuclear antigens and abnormal activation of self-reactive T and B cells lead to self-antibodies and immune complex production. The autoreactive lymphocytes are removed by the apoptotic process in healthy individuals; however, apoptosis disruption could cause accumulation of apoptotic bodies and nuclear debris. Therefore, apoptosis plays a crucial role in the pathogenesis of autoimmune diseases...
July 4, 2017: Postgraduate Medical Journal
https://www.readbyqxmd.com/read/28665157/sex-related-differences-in-autoimmune-induced-lung-lesions-in-mrl-mpj-fas-lpr-mice-are-mediated-by-the-development-of-mediastinal-fat-associated-lymphoid-clusters
#7
Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
MRL/MpJ-Fas(lpr) (lpr) mice are a model for autoimmune diseases such as systemic lupus erythematosus (SLE). These diseases mainly affect women, with a 10:1 female-to-male ratio, and cause pleuropulmonary lesions. We previously revealed a correlation between mediastinal fat-associated lymphoid cluster (MFALC) development and cellular infiltration in the lungs of lpr male mice; however, we did not report on MFALCs in females. The purpose of this investigation was to reveal sex-related differences in MFALCs in lpr mice...
June 30, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#8
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28631301/prevention-of-lupus-nephritis-development-in-nzb-nzw-mice-by-selective-blockade-of-cd28
#9
Laetitia Laurent, Awena Lefur, Rozenn Le Bloas, Mélanie Néel, Caroline Mary, Anne Moreau, Nicolas Poirier, Bernard Vanhove, Fadi Fakhouri
Systemic Lupus Erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG...
June 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28623084/pathogenesis-of-human-systemic-lupus-erythematosus-a-cellular-perspective
#10
REVIEW
Vaishali R Moulton, Abel Suarez-Fueyo, Esra Meidan, Hao Li, Masayuki Mizui, George C Tsokos
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors...
July 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28605137/peripheral-immunophenotyping-identifies-three-subgroups-based-on-t-cell-heterogeneity-in-lupus-patients
#11
Satoshi Kubo, Shingo Nakayamada, Maiko Yoshikawa, Yusuke Miyazaki, Kei Sakata, Kazuhisa Nakano, Kentaro Hanami, Shigeru Iwata, Ippei Miyagawa, Kazuyoshi Saito, Yoshiya Tanaka
OBJECTIVE: To elucidate the diversity of systemic lupus erythematosus (SLE), we stratified active SLE patients based on immunophenotyping. METHODS: Peripheral blood mononuclear cells were obtained from 143 SLE patients and 49 healthy individuals. Circulating B, T and dendritic cells were defined based on flow cytometric analysis for human immune system termed "the Human Immunology Project". Based on these results, the immunophenotype was visualized by principal component analysis and SLE patients classified into subgroups by cluster analysis...
June 12, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28539549/the-metabolic-regulation-in-immune-cells-and-pathogenesis-of-systemic-lupus-erythematosus-%C3%A2-toward-new-therapeutic-applications%C3%A2
#12
Yusuke Takeshima, Yukiko Iwasaki, Tomohisa Okamura, Keishi Fujio, Kazuhiko Yamamoto
  The importance of cellular metabolism has long been known as Warburg effect; cancer cells are characterized by mitochondrial defect that shifts towards aerobic glycolysis. Recently, many reports have revealed that immune metabolism is a key factor for controlling immune cell proliferation and differentiation. Resting lymphocytes generate energy through oxidative phosphorylation and fatty acid oxidation, whereas activated lymphocytes rapidly shift to glycolysis. Especially in T cells, more precise mechanism of regulating metabolism have been clarified on differentiation from naïve T cells to effector T cells...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28534426/the-immunological-personality-of-close-relatives-of-sle-patients
#13
M R Salaman, D A Isenberg
Immunological abnormalities seen in relatives of patients with autoimmune disorders can be useful in understanding the pathogenesis of the disease since, unlike in patients, they cannot result from the disease process or drug treatment. In this article we present a brief overview of our studies of the basic immunological status of close relatives of SLE patients. We looked at blood levels of IgG, IgM and antibodies to double-stranded DNA, as well as at NK cell numbers and cytotoxic activity and the levels of NKT, B and T cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28500565/dysregulated-lymphoid-cell-populations-in-mouse-models-of-systemic-lupus-erythematosus
#14
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/28471497/haploinsufficiency-of-nadph-oxidase-subunit-neutrophil-cytosolic-factor-2-is-sufficient-to-accelerate-full-blown-lupus-in-nzm-2328-mice
#15
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 the gene for neutrophil cytosolic factor 2 (NCF-2) predisposes to lupus, and we have identified lupus patients with point mutations that are predicted to cause reduced NADPH oxidase activity. We undertook this study to investigate the relationship between reduced leukocyte NADPH oxidase activity and immune dysregulation associated with systemic lupus erythematosus (SLE). METHODS: We generated NCF-2-null mice, in which NADPH oxidase activity is absent, on the nonautoimmune C57BL/6 (B6) mouse background and on the NZM 2328 mouse background, a polygenic model in which mice spontaneously develop lupus...
May 4, 2017: Arthritis & Rheumatology
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
#16
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
#17
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
#18
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/28400152/anti-cd3-antibody-therapy-attenuates-the-progression-of-hypertension-in-female-mice-with-systemic-lupus-erythematosus
#19
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
#20
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
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