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https://www.readbyqxmd.com/read/27917174/cd16-monocyte-subset-was-enriched-and-functionally-exacerbated-in-driving-t-cell-activation-and-b-cell-response-in-systemic-lupus-erythematosus
#1
Huaqun Zhu, Fanlei Hu, Xiaolin Sun, Xiaoying Zhang, Lei Zhu, Xu Liu, Xue Li, Liling Xu, Lianjie Shi, Yuzhou Gan, Yin Su
BACKGROUND: The roles that CD16(+) monocyte subset plays in T-cell activation and B-cell response have not been well studied in systemic lupus erythematosus (SLE). OBJECTIVE: The present study aimed to investigate the distribution of CD16(+) monocyte subsets in SLE and explore their possible roles in T-cell activation and B-cell differentiation. METHODS: The frequencies of monocyte subsets in the peripheral blood of healthy controls (HCs) and patients with SLE were determined by flow cytometry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#2
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27906046/chromatin-landscapes-and-genetic-risk-in-systemic-lupus
#3
Joyce S Hui-Yuen, Lisha Zhu, Lai Ping Wong, Kaiyu Jiang, Yanmin Chen, Tao Liu, James N Jarvis
BACKGROUND: Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27818202/the-expression-of-bcl-6-in-circulating-follicular-helper-like-t-cells-positively-correlates-with-the-disease-activity-in-systemic-lupus-erythematosus
#4
Xin Huang, Haijing Wu, Hong Qiu, Huilan Yang, Yaxiong Deng, Ming Zhao, Hairong Luo, Xiang Zhou, Yubin Xie, Vera Chan, Chak-Sing Lau, Qianjin Lu
Increased circulating follicular helper-like T cells (cTfh) are reported in systemic lupus erythematosus (SLE) patients. However, whether B-cell lymphoma 6 (Bcl-6) is expressed in cTfh cells remains to be clarified. In this study, we found that the frequencies of CD4(+)CXCR5(hi)PD-1(hi)cTfh, CD4(+)CXCR5(hi)PD-1(hi)ICOS(hi), and CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) populations were significantly increased in SLE patients (n=70) when compared with healthy controls (n=48). Surprisingly, only CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) cTfh cells, rather than CD4(+)CXCR5(hi)PD-1(hi) population, were positively correlated with SLEDAI and anti-dsDNA antibodies...
November 3, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27812954/activation-of-the-mechanistic-target-of-rapamycin-in-sle-explosion-of-evidence-in-the-last-five-years
#5
REVIEW
Zachary Oaks, Thomas Winans, Nick Huang, Katalin Banki, Andras Perl
The mechanistic target of rapamycin (mTOR) is a central regulator in cell growth, activation, proliferation, and survival. Activation of the mTOR pathway underlies the pathogenesis of systemic lupus erythematosus (SLE). While mTOR activation and its therapeutic reversal were originally discovered in T cells, recent investigations have also uncovered roles in other cell subsets including B cells, macrophages, and "non-immune" organs such as the liver and the kidney. Activation of mTOR complex 1 (mTORC1) precedes the onset of SLE and associated co-morbidities, such as anti-phospholipid syndrome (APS), and may act as an early marker of disease pathogenesis...
December 2016: Current Rheumatology Reports
https://www.readbyqxmd.com/read/27769564/in-vivo-anti-inflammatory-activities-of-novel-cytokine-il-38-in-murphy-roths-large-mrl-lpr-mice
#6
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
October 17, 2016: Immunobiology
https://www.readbyqxmd.com/read/27733759/beyond-pan-b-cell-directed-therapy-new-avenues-and-insights-into-the-pathogenesis-of-sle
#7
Thomas Dörner, Peter E Lipsky
New insights into the mechanisms of autoimmune diseases have been obtained not only from preclinical studies, but also from clinical trials of pan-B-cell-directed therapy. Overall, the results of these clinical trials suggest that more-specific approaches focusing on pathogenic B-cell functions, and perhaps sparing or even enhancing regulatory B-cell activity, might be attractive alternatives. Importantly, pathogenic B-cell subpopulations function within a network of cellular interactions, many of which might require additional interventions to restore immunologic balance and suppress autoimmune disease...
October 13, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27723281/gene-expression-and-pharmacodynamic-induced-changes-in-1-760-sle-patients-from-two-phase-iii-trials-of-b-cell-activating-factor-blockade-with-tabalumab
#8
Robert W Hoffman, Joan T Merrill, Marta M E Alarcón-Riquelme, Michelle Petri, Ernst R Dow, Eric Nantz, Laura K Nisenbaum, Krista M Schroeder, Wendy J Komocsar, Narayanan B Perumal, Matthew D Linnik, David C Airey, Yushi Liu, Guilherme V Rocha, Richard E Higgs
OBJECTIVE: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. METHODS: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors...
October 9, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27697141/follicular-t-helper-cells-and-il-21-in-rheumatic-diseases
#9
Tue Kruse Rasmussen
Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are lifelong diseases with increased mortality and chronic pains. They are both characterized by immunological imbalances causing the immune system attack and destroy the bodies own tissues (called autoimmune disease). The best treatment, we are currently able to offer these patients, cause significant side-effects and can not prevent significant loss of quality of life. At the heart of the disease mechanisms in RA and SLE are subsets of immune cells called T and B cells...
October 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27687023/biological-therapies-in-the-treatment-of-cutaneous-lupus-erythematosus
#10
J K Presto, E Z Hejazi, V P Werth
Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease occurring in association with or without systemic lupus erythematosus (SLE). Although antimalarials are widely used as the first-line systemic agent, refractory cases may benefit from additional immunomodulators, immunosuppressives, and biologics. An interest in biological therapies for CLE has emerged in recent years due to novel insight into the pathogenesis of CLE. These targets include B cells, T cells, and cytokines that are involved in immune system pathways...
September 29, 2016: Lupus
https://www.readbyqxmd.com/read/27635407/follicular-helper-t-cells-in-systemic-lupus-erythematosus-why-should-they-be-considered-as-interesting-therapeutic-targets
#11
REVIEW
Matthieu Sawaf, Hélène Dumortier, Fanny Monneaux
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell hyperactivity leading to the production of autoantibodies, some of which having a deleterious effect. Reducing autoantibody production thus represents a way of controlling lupus pathogenesis, and a better understanding of the molecular and cellular factors involved in the differentiation of B cells into plasma cells could allow identifying new therapeutic targets. Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B cells...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27600904/the-transcriptional-repressor-gfi1-prevents-lupus-autoimmunity-by-restraining-tlr7-signaling
#12
Benoit Desnues, Amanda B Macedo, Diana Ordoñez-Rueda, Annie Roussel-Queval, Bernard Malissen, Pierre Bruhns, Marie Malissen, Lena Alexopoulou
The transcriptional repressor growth factor independence 1 (Gfi1) is important in myeloid and lymphoid differentiation. In the current study we evaluated the involvement of Gfi1 in systemic lupus erythematosus (SLE). We found that Genista mice, which carry a hypomorphic mutation in the gfi1 gene or Gfi1-deficient (Gfi1(-/-) ) mice develop signs of spontaneous lupus autoimmunity, including increased serum levels of IgM and IgG2a, autoantibodies against RNA and DNA, glomerular immunodeposits and increased frequencies of plasmablasts, germinal center (GC) B cells and age-associated B cells (ABCs)...
September 7, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27592380/from-old-concerns-to-new-advances-and-personalized-medicine-in-lupus-the-end-of-the-tunnel-is-approaching
#13
Andrea Doria, M Eric Gershwin, Carlo Selmi
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity...
August 31, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27590046/impact-of-heart-rate-variability-a-marker-for-cardiac-health-on-lupus-disease-activity
#14
Aikaterini Thanou, Stavros Stavrakis, John W Dyer, Melissa E Munroe, Judith A James, Joan T Merrill
BACKGROUND: Decreased heart rate variability (HRV) is associated with adverse outcomes in cardiovascular diseases and has been observed in patients with systemic lupus erythematosus (SLE). We examined the relationship of HRV with SLE disease activity and selected cytokine pathways. METHODS: Fifty-three patients from the Oklahoma Lupus Cohort were evaluated at two visits each. Clinical assessments included the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group (BILAG) index, physician global assessment (PGA), and Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index...
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27576056/novel-molecular-signatures-in-mononuclear-cell-populations-from-patients-with-systemic-lupus-erythematosus
#15
Mikhail Olferiev, Elzbieta Jacek, Kyriakos A Kirou, Mary K Crow
To gain novel insights into the immunopathogenesis of systemic lupus erythematosus we have analyzed gene expression data from isolated CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD56(+) NK-cell enriched peripheral blood cell fractions from patients and healthy donors. As predicted, type I interferon-inducible gene transcripts are overexpressed in all populations. Transcripts preferentially expressed in SLE CD4(+) and CD8(+) T cells include those associated with Tregulatory and Th17 effector cell programs, respectively, but in each case additional transcripts predicted to limit differentiation of those effector cells are detected...
August 26, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27540538/value-of-foxp3-expressing-t-regulatory-cells-in-renal-tissue-in-lupus-nephritis-an-immunohistochemical-study
#16
Marwa M Shakweer, Maha Behairy, Nadia G Elhefnawy, Tamer W Elsaid
BACKGROUND: Forkhead box P3 (Foxp3) functions as a master regulator in the development and function of T-regulatory (Treg) cells. Recent studies have shown that autoimmune diseases including systemic lupus erythematosus (SLE) are associated with an imbalance with the Treg cells and T helper (Th) subtypes. OBJECTIVES: To evaluate immunohistochemical expression of Foxp3 positive Treg cells in lupus nephritis (LN) and analyze its association with clinicopathologic parameters...
July 2016: Journal of Nephropathology
https://www.readbyqxmd.com/read/27497254/interferon-targeted-therapy-in-systemic-lupus-erythematosus-is-this-an-alternative-to-targeting-b-and-t-cells
#17
K C Kalunian
Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE...
September 2016: Lupus
https://www.readbyqxmd.com/read/27497252/t-cell-directed-therapies-in-systemic-lupus-erythematosus
#18
P Nandkumar, R Furie
Drug development for the treatment of systemic lupus erythematosus (SLE) has largely focused on B-cell therapies. A greater understanding of the immunopathogenesis of SLE coupled with advanced bioengineering has allowed for clinical trials centered on other targets for SLE therapy. The authors discuss the benefits and shortcomings of focusing on T-cell-directed therapies in SLE and lupus nephritis clinical trials.
September 2016: Lupus
https://www.readbyqxmd.com/read/27436361/rock2-signaling-is-required-to-induce-a-subset-of-t-follicular-helper-cells-through-opposing-effects-on-stats-in-autoimmune-settings
#19
Jonathan M Weiss, Wei Chen, Melanie S Nyuydzefe, Alissa Trzeciak, Ryan Flynn, James R Tonra, Suzana Marusic, Bruce R Blazar, Samuel D Waksal, Alexandra Zanin-Zhorov
Rho-associated kinase 2 (ROCK2) determines the balance between human T helper 17 (TH17) cells and regulatory T (Treg) cells. We investigated its role in the generation of T follicular helper (TFH) cells, which help to generate antibody-producing B cells under normal and autoimmune conditions. Inhibiting ROCK2 in normal human T cells or peripheral blood mononuclear cells from patients with active systemic lupus erythematosus (SLE) decreased the number and function of TFH cells induced by activation ex vivo. Moreover, inhibition of ROCK2 activity decreased the abundance of the transcriptional regulator Bcl6 (B cell lymphoma 6) and increased that of Blimp1 by reducing the binding of signal transducer and activator of transcription 3 (STAT3) and increasing that of STAT5 to the promoters of the genes Bcl6 and PRDM1, respectively...
2016: Science Signaling
https://www.readbyqxmd.com/read/27424138/evaluation-of-pbmc-distribution-and-tlr9-expression-in-patients-with-systemic-lupus-erythematosus
#20
Sahar Mortezagholi, Zohreh Babaloo, Parisa Rahimzadeh, Mojgan Ghaedi, Hayedeh Namdari, Shirin Assar, Maryam Azimi Mohamadabadi, Eisa Salehi
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which results in damage to various organs. Some animal studies have revealed that activation of Toll-like receptors (TLRs) is important in the pathogenesis of SLE. In the present study, the percentage of different immune cell subsets in 35 SLE patients and 38 control subjects was analyzed by flow cytometry. We also assessed the expression of TLR9 in the population of peripheral blood mononuclear cells (PBMCs) including T lymphocytes (CD4+ and CD8+), B lymphocytes (CD19+), NK cells (CD56+) and monocytes (CD14+) in SLE patients and healthy controls...
June 2016: Iranian Journal of Allergy, Asthma, and Immunology
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