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SLE AND T cells

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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
#1
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
#2
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/27904655/increased-set1-binding-at-the-promoter-induces-aberrant-epigenetic-alterations-and-up-regulates-cyclic-adenosine-5-monophosphate-response-element-modulator-alpha-in-systemic-lupus-erythematosus
#3
Qing Zhang, Shu Ding, Huilin Zhang, Hai Long, Haijing Wu, Ming Zhao, Vera Chan, Chak-Sing Lau, Qianjin Lu
BACKGROUND: Up-regulated cyclic adenosine 5'-monophosphate response element modulator α (CREMα) which can inhibit IL-2 and induce IL-17A in T cells plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). This research aimed to investigate the mechanisms regulating CREMα expression in SLE. RESULTS: From the chromatin immunoprecipitation (ChIP) microarray data, we found a sharply increased H3 lysine 4 trimethylation (H3K4me3) amount at the CREMα promoter in SLE CD4+ T cells compared to controls...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27894401/association-between-the-cytotoxic-t-lymphocyte-antigen-4-mutations-and-the-susceptibility-to-systemic-lupus-erythematosus-contribution-markers-of-inflammation-and-oxidative-stress
#4
M Tanhapour, A Vaisi-Raygani, F Bahrehmand, M Khazaei, A Kiani, Z Rahimi, H Nomani, H Tavilani, T Pourmotabbed
: The cytotoxic T lymphocyte antigen-4 (CTLA-4) also known as CD152 (cluster of differentiation 152) is a crucial negative regulator of the immune system. This protein receptor provides negative signals in order to suppress T-cell activation and immune attack against self-antigens, although its role is unclear.  The ability of CTLA-4 to limit T cell-mediated immune response has made it a major target in treatment of tumors and autoimmune diseases such as systemic lupus erythematosus (SLE)...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27887663/effects-of-royal-jelly-supplementation-on-regulatory-t-cells-in-children-with-sle
#5
Asmaa M Zahran, Khalid I Elsayh, Khaled Saad, Esraa M A Eloseily, Naglaa S Osman, Mohamd A Alblihed, Gamal Badr, Mohamed H Mahmoud
BACKGROUND AND OBJECTIVE: To our knowledge, no previous studies have focused on the immunomodulatory effects of fresh royal jelly (RJ) administration on systemic lupus erythematosus (SLE) in humans. Our aim was to study the effect of fresh RJ administration on the disease course in children with SLE with some immunological markers (CD4(+) and CD8(+) regulatory T cells and T lymphocytes apoptosis). METHODS: This was an open-label study in which 20 SLE children received 2 g of freshly prepared RJ daily, for 12 weeks...
2016: Food & Nutrition Research
https://www.readbyqxmd.com/read/27882473/foxp3-regulatory-t-cell-and-autoimmune-diseases
#6
REVIEW
Jin-Hui Tao, Miao Cheng, Jiang-Ping Tang, Qin Liu, Fan Pan, Xiang-Pei Li
Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases. Therefore, therapeutic modulation of Tregs could be a potent means of treating autoimmune diseases. Human Tregs are diverse, however, and not all of them have immunosuppressive effects. Forkhead box P3 (Foxp3), a pivotal transcription factor of Tregs that is crucial in maintaining Treg immunosuppressive function, can be expressed heterogeneously or unstably across Treg subpopulations...
November 24, 2016: Inflammation
https://www.readbyqxmd.com/read/27881354/-analysis-of-immune-suppression-in-patients-with-systemic-lupus-erythematosus-complicated-by-herpes-zoster-virus-infection
#7
Hui Ouyang, Xue-Chang He, Yi Zhou, Zhao-Xia Li
OBJECTIVE: To explore the changes in cellular immune function and the safety of physical therapy in patients with systemic lupus erythematosus (SLE) complicated by herpes zoster (HZ) virus infection. Methods A retrospective analysis was conducted among 10 SLE pateints with HZ virus infection, with 30 SLE patients without HZ infection as the control group. The results of routine laboratory tests and T lymphocyte subset counts (before and during infection and after cure of infection) were compared between the two groups...
November 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27880975/ror%C3%AE-t-expression-in-tregs-promotes-systemic-lupus-erythematosus-via-il-17-secretion-alteration-of-treg-phenotype-and-suppression-of-th2-responses
#8
Malte A Kluger, Anna Nosko, Torben Ramcke, Boeren Goerke, Matthias C Meyer, Claudia Wegscheid, Michael Luig, Gisa Tiegs, Rolf A K Stahl, Oliver M Steinmetz
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immuno-pathogenesis. However, a pathogenic role for the Th17 axis was demonstrated by many studies, while Tregs were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both, the Treg characteristic transcription factor Foxp3 and the Th17 defining RORγt. Studies in a model of acute glomerulonephritis unveiled potent regulatory, but in addition also pro-inflammatory functions of RORγt(+) Foxp3(+) Tregs...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27880973/immunopathogenesis-of-systemic-lupus-erythematosus-and-rheumatoid-arthritis-the-role-of-aberrant-expression-of-non-coding-rnas-in-t-cells
#9
REVIEW
Ning-Sheng Lai, Malcolm Koo, Chia-Li Yu, Ming-Chi Lu
Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are RNA molecules that do not translate into protein. Both miRNAs and lncRNAs are known to regulate gene expression and to play an essential role in T cell differentiation and function. Both systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease, and rheumatoid arthritis (RA), a representative disease of inflammatory arthritis, are characterized by a complex dysfunction in the innate and adaptive immunity...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27856665/emerging-roles-of-egr2-and-egr3-in-the-control-of-systemic-autoimmunity
#10
REVIEW
Kaoru Morita, Tomohisa Okamura, Shuji Sumitomo, Yukiko Iwasaki, Keishi Fujio, Kazuhiko Yamamoto
SLE is an autoimmune disease characterized by multiple organ damage mediated by autoantibodies and autoreactive T cells. Approaches utilizing genetically engineered mice as well as genome-wide association studies have identified a number of lupus-related genes. Recently, early growth response gene 2 (Egr2) and Egr3 have emerged as regulatory molecules that suppress excessive immune responses. Mice deficient for Egr2 and Egr3 develop a lupus-like disease with dysregulated activation of effector T cells. Furthermore, Egr2 and Egr3 confer suppressive activity to CD4(+) T cells and regulate the production of inhibitory cytokines such as IL-10 and TGF-β1...
December 2016: Rheumatology
https://www.readbyqxmd.com/read/27852285/elevated-expression-of-mir-142-3p-is-related-to-the-pro-inflammatory-function-of-monocyte-derived-dendritic-cells-in-sle
#11
Yilun Wang, Jun Liang, Haihong Qin, Yan Ge, Juan Du, Jinran Lin, Xiaohua Zhu, Jie Wang, Jinhua Xu
BACKGROUND: Recent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of the alteration remains unclear. METHODS: We cultured monocyte-derived DCs (moDCs) in vitro and examined the cytokines and chemokines in the supernatants of moDCs in negative controls (NC) and SLE patients in active phase. We then profiled microRNAs (miRNAs) of LPS-stimulated moDCs in SLE patients and used real-time PCR to verify the differentially expressed miRNAs...
November 16, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27848183/an-atypical-case-of-late-onset-systemic-lupus-erythematosus-with-systemic-lymphadenopathy-and-severe-autoimmune-thrombocytopenia-neutropenia-mimicking-malignant-lymphoma
#12
Keita Tamaki, Satoko Morishima, Sawako Nakachi, Sakiko Kitamura, Sachie Uchibori, Shouhei Tomori, Taeko Hanashiro, Natsuki Shimabukuro, Iori Tedokon, Kazuho Morichika, Yukiko Nishi, Takeaki Tomoyose, Kennosuke Karube, Takuya Fukushima, Hiroaki Masuzaki
Here, we report a rare case of systemic lupus erythematosus (SLE) with conspicuous manifestation of hematological abnormalities. At onset, the 52-year-old male patient showed systemic lymphadenopathy and splenomegaly, severe autoimmune thrombocytopenia, and autoimmune neutropenia. Bone marrow examination and lymph node biopsy excluded the possibility of malignant lymphoma. Based on laboratory findings, he was finally diagnosed with combined autoimmune cytopenia coupled with SLE. Atypical clinical manifestations of SLE prompted us to explore the possibility of autoimmune lymphoproliferative syndrome (ALPS)...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27847409/effect-of-interleukin-15-on-cd11b-cd54-and-cd62l-expression-on-natural-killer-cell-and-natural-killer-t-like-cells-in-systemic-lupus-erythematosus
#13
Syh-Jae Lin, Ji-Yih Chen, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Jing-Long Huang
Adhesion molecules may play an important role in systemic lupus erythematosus (SLE) pathogenesis. We investigated the effect of interleukin- (IL-) 15 on CD11b, CD54, and CD62L expression on natural killer (NK) cells, T cells, and CD56(+)CD3(+) NKT-like cells from SLE subjects and healthy controls. SLE patients had decreased circulating NK cells and NKT-like cells compared to controls. NK cells from SLE patients showed higher CD11b and CD62L expression compared to controls. IL-15 enhanced CD11b and CD54 but downregulated CD62L expression on NK cells from SLE patients...
2016: Mediators of Inflammation
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
#14
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
#15
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/27784388/-imbalance-of-tc-and-th-in-peripheral-blood-of-patients-with-systemic-lupus-erythematosus-and-its-significance
#16
Wei-Jun Gu, Qing-Guo Zhang, Wei Zhu, Yu-Lin Guo, Lu-Qin Zhang
OBJECTIVE: To investigate the imbalance of Tc1/Tc2,Th1/Th2 and Tc/Th in patients with systemic lupus erythematosus(SLE) and its relationship with the clinical stages of SLE. METHODS: The full blood culture and flow cytometry with fluorescence-labelled T lymphocytes were used to detect the levels of T-lymphocyte subsets and its intracellular factors IFN-γ and IL-4 in peripheral blood from SLP patients in active, inactive stages and normal healthy persons as controls, to compare the changes of Tc1,Tc2; Th1,Th2 levels and Tc/Th ratio in SLP patients in active and inactive stages, and to analyze their relationship with SLEDAI staging...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27781205/a-unique-cause-of-proteinuria-in-pregnancy-class-ii-lupus-nephritis-with-concomitant-minimal-change-disease
#17
Ryan Kunjal, Rabie Adam-Eldien, Raafat Makary, Francois Jo-Hoy, Charles W Heilig
We report the case of a 22-year-old African American female who presented to another facility for routine follow-up in the 34th week of pregnancy with lower extremity swelling and nephrotic-range proteinuria. Although she was normotensive, it was initially thought that she had preeclampsia. She was monitored carefully and delivery was induced at 37 weeks of gestation. She was transferred to our hospital, where she was diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria...
September 2016: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/27777414/microparticles-in-the-blood-of-patients-with-systemic-lupus-erythematosus-sle-phenotypic-characterization-and-clinical-associations
#18
Fariborz Mobarrez, Anna Vikerfors, Johanna T Gustafsson, Iva Gunnarsson, Agneta Zickert, Anders Larsson, David S Pisetsky, Håkan Wallén, Elisabet Svenungsson
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27770825/suppression-of-lupus-nephritis-and-skin-lesions-in-mrl-lpr-mice-by-administration-of-the-topoisomerase-i-inhibitor-irinotecan
#19
Andreas Keil, Sean R Hall, Meike Körner, Martin Herrmann, Ralph A Schmid, Steffen Frese
BACKGROUND: Since the precise mechanism for the pathogenesis of systemic lupus erythematosus (SLE) is unknown, no targeted therapies in addition to immunosuppression are available so far. We recently demonstrated that administration of the topoisomerase I (topo I) inhibitor irinotecan at extremely low concentrations reversed established lupus nephritis in NZB/NZW mice. While profound immunosuppression was absent, we proposed changes in DNA relaxation and anti-double-stranded (ds)DNA antibody binding as the underlying mechanism...
October 22, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27769564/in-vivo-anti-inflammatory-activities-of-novel-cytokine-il-38-in-murphy-roths-large-mrl-lpr-mice
#20
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
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