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SLE AND T cells

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https://www.readbyqxmd.com/read/28076903/slamf7-engagement-restores-defective-effector-cd8-t-cells-activity-in-response-to-foreign-antigens-in-systemic-lupus-erythematosus
#1
Denis Comte, Maria P Karampetsou, Nobuya Yoshida, Katalin Kis-Toth, Vasileios C Kyttaris, George C Tsokos
OBJECTIVE: Effector CD8+ T cell function is impaired in SLE and associated with compromised ability to fight infections. SLAMF7 engagement has been shown to enhance NK cell degranulation. Thus, we characterized the expression and function of SLAMF7 on CD8+ T cells subsets isolated from peripheral blood of SLE patients and healthy subjects. METHODS: CD8+ T cell subset distribution, SLAMF7 expression and cytolytic enzyme expression (perforin, GzmA, GzmB) were monitored on cells isolated from SLE patients and healthy controls by flow cytometry...
January 11, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28063160/elevated-semaphorin5a-in-systemic-lupus-erythematosus-is-in-association-with-disease-activity-and-lupus-nephritis
#2
Yan Du, Xinyu Wu, Mo Chen, Wenwen Wang, Weihong Xv, Lv Ye, Di Wu, Jing Xue, Wenjia Sun, Judong Luo, Huaxiang Wu
OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by extensive immune response including over-activation of T and B cells development of pathogenic autoantibodies, organ damage induced by the formation and deposition of immune complex, and the abnormal elevation of type I interferon. Semaphorin5A (Sema5A), is essentially involved in immune cell regulation and also implicated in the pathogenesis of autoimmune disorders. We aimed to evaluate the role of Sema5A in patients with SLE...
January 7, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28062664/mapping-eqtls-with-rna-seq-reveals-novel-susceptibility-genes-non-coding-rnas-and-alternative-splicing-events-in-systemic-lupus-erythematosus
#3
Christopher A Odhams, Andrea Cortini, Lingyan Chen, Amy L Roberts, Ana Viñuela, Alfonso Buil, Kerrin S Small, Emmanouil T Dermitzakis, David L Morris, Timothy J Vyse, Deborah S Cunninghame Graham
Studies attempting to functionally interpret complex-disease susceptibility loci by GWAS and eQTL integration have predominantly employed microarrays to quantify gene-expression. RNA-Seq has the potential to discover a more comprehensive set of eQTLs and illuminate the underlying molecular consequence. We examine the functional outcome of 39 variants associated with Systemic Lupus Erythematosus (SLE) through integration of GWAS and eQTL data from the TwinsUK microarray and RNA-Seq cohort in lymphoblastoid cell lines...
January 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28045014/death-receptor-6-contributes-to-autoimmunity-in-lupus-prone-mice
#4
Daisuke Fujikura, Masahiro Ikesue, Tsutomu Endo, Satoko Chiba, Hideaki Higashi, Toshimitsu Uede
Expansion of autoreactive follicular helper T (Tfh) cells is tightly restricted to prevent induction of autoantibody-dependent immunological diseases, such as systemic lupus erythematosus (SLE). Here we show expression of an orphan immune regulator, death receptor 6 (DR6/TNFRSF21), on a population of Tfh cells that are highly expanded in lupus-like disease progression in mice. Genome-wide screening reveals an interaction between syndecan-1 and DR6 resulting in immunosuppressive functions. Importantly, syndecan-1 is expressed specifically on autoreactive germinal centre (GC) B cells that are critical for maintenance of Tfh cells...
January 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28040536/th9-cells-and-il-9-in-autoimmune-disorders-pathogenesis-and-therapeutic-potentials
#5
REVIEW
Yaxiong Deng, Zijun Wang, Christopher Chang, Liwei Lu, Chak Sing Lau, Qianjin Lu
Naïve CD4(+) T cells are pleiotropically divided into various T helper (Th) cell subsets, according to their pivotal roles in the regulation of immune responses. The differentiation of Th9 cells, an interleukin (IL)-9 producing subset, can be impacted by specific environmental cues, co-stimulation with transforming growth factor β (TGF-β) and IL-4, and other regulatory factors. Although IL-9 has been recognized as a classical Th2-related cytokine, recent studies have indicated that IL-9-producing cells contribute to a group of autoimmune disorders including systemic lupus erythematosus (SLE), multiple sclerosis (MS), inflammatory bowel diseases (IBD), rheumatoid arthritis (RA) and psoriasis...
December 28, 2016: Human Immunology
https://www.readbyqxmd.com/read/28031442/decreased-platelet-size-is-associated-with-platelet-activation-and-anti-phospholipid-syndrome-in-systemic-lupus-erythematosus
#6
Christian Lood, Helena Tydén, Birgitta Gullstrand, Christoffer T Nielsen, Niels H H Heegaard, Petrus Linge, Andreas Jönsen, Roger Hesselstrand, Robin Kahn, Anders A Bengtsson
OBJECTIVES: SLE is an autoimmune disease with increased cardiovascular morbidity and platelet activation. In the general population, increased platelet size predicts platelet reactivity and cardiovascular disease. The aim of this study was to investigate whether platelet size related to platelet activation and cardiovascular disease in SLE. METHODS: Fresh blood samples from SLE patients (n = 148), healthy volunteers (n = 79) and disease controls (n = 40) were analysed for platelet size and activation by flow cytometry, ELISA and cell count...
December 27, 2016: Rheumatology
https://www.readbyqxmd.com/read/27996081/tolerogenic-probiotics-potential-immunoregulators-in-systemic-lupus-erythematosu
#7
REVIEW
Seyed Alirezae Esmaeili, Mahmoud Mahmoudi, Amir Abbas Momtazi-Borojeni, Amirhossein Sahebkar, Hassan Doulabi, Maryam Rastin
Probiotics are commensal or nonpathogenic microbes that colonize the gastrointestinal tract and confer beneficial effects on the host through several mechanisms such as competitive exclusion, anti-bacterial effects, and modulation of immune responses. There is growing evidence supporting the immunomodulatory ability of some probiotics. Several experimental and clinical studies have been shown beneficial effect of some probiotic bacteria, particularly Lactobacillus and Bifidobacteria strains, on inflammatory and autoimmune diseases...
December 20, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27993973/anaplasma-marginale-outer-membrane-protein-a-is-an-adhesin-that-recognizes-sialylated-and-fucosylated-glycans-and-functionally-depends-on-an-essential-binding-domain
#8
Kathryn S Hebert, David Seidman, Aminat T Oki, Jerilyn Izac, Sarvani Emani, Lee D Oliver, Daniel P Miller, Brittney K Tegels, Reiji Kannagi, Richard T Marconi, Jason A Carlyon
Anaplasma marginale causes bovine anaplasmosis, a debilitating and potentially fatal tick-borne infection of cattle. Because A. marginale is an obligate intracellular organism, its adhesins that mediate entry into host cells are essential for survival. Here, we demonstrate that A. marginale outer membrane protein A (AmOmpA; AM854) contributes to the invasion of mammalian and tick host cells. AmOmpA exhibits predicted structural homology to OmpA of A. phagocytophilum (ApOmpA), an adhesin that uses key lysine and glycine residues to interact with α2,3-sialylated and α1,3-fucosylated glycan receptors, including 6-sulfo-sialyl Lewis x...
December 19, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27992697/vista-deficiency-accelerates-the-development-of-fatal-murine-lupus-nephritis
#9
Sabrina Ceeraz, Petra A Sergent, Sean F Plummer, Alan R Schned, Dov Pechenick, Christopher M Burns, Randolph J Noelle
OBJECTIVES: The targeting of negative checkpoint regulators (NCRs) as a means of augmenting anti-tumor immune responses is now an increasingly utilized and remarkably effective approach to the treatment of several human malignancies. The NCR VISTA (V-domain Ig suppressor of T cell activation, PD-1H, DD1α) suppresses T cell responses and regulates myeloid activities. We proposed that exploitation of the VISTA pathway is a novel strategy for the treatment of human autoimmune disease and therefore studied the impact of VISTA genetic deficiency on lupus development in a lupus-prone mouse strain...
December 19, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27992687/cd4-t-cells-from-sle-patients-respond-poorly-to-exogenous-il-2
#10
Denis Comte, Maria P Karampetsou, Katalin Kis-Toth, Nobuya Yoshida, Sean J Bradley, Vasileios C Kyttaris, George C Tsokos
Objective Imbalanced cytokine production by T cells characterizes both patients with SLE and lupus-prone mice and contributes to immune dysregulation. In this study, we further characterize in detail the production of IL-2, IFNγ, IL-4 and IL-17A by CD4+ subsets in healthy subjects and SLE patients and the signaling response of CD4+ T cells in response to exogenous IL-2. Methods Cytokine production by CD4+ T cell differentiated subsets was assessed by intracellular staining following stimulation with phorbol myristate acetate and ionomycin and by ELISA after anti-CD3/anti-CD28 stimulation...
December 19, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27987522/-interleukin-2-signaling-pathway-regulating-molecules-in-systemic-lupus-erythematosus
#11
Q Guo, X Y Chen, Y Su
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease, which characterized by complex immunological abnormalities and multiple tissue and organ damages. The etiology and pathogenesis of SLE have not been entirely recognized. Genetic, environmental and viral infections and other factors might be related to the pathogenetic mechanisms of SLE. Interleukin-2 (IL-2) is a critical cytokine produced by T cells upon activation and is important for the generation of T regulatory cells and activation-induced cell death...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27965465/decreased-g%C3%AE-q-expression-in-t-cells-correlates-with-enhanced-cytokine-production-and-disease-activity-in-systemic-lupus-erythematosus
#12
Yan He, Yan Huang, Lei Tu, Jiao Luo, Bing Yu, Hongyan Qian, Lihua Duan, Guixiu Shi
Aberrant T cell immune responses appear central to the development of systemic lupus erythematosus (SLE). We previously reported that Gαq, the alpha subunit of Gq, regulates T and B cell immune responses, promoting autoimmunity. To address whether Gαq contributes to the pathogenesis of SLE, Gαq mRNA expression was studied using real time-PCR in PBMCs and T cells from SLE patients as well as age- and sex-matched healthy controls. Our results showed that Gαq mRNA expression was decreased in PBMCs and T cells from SLE patients compared to healthy individuals...
December 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27940592/cd3z-hypermethylation-is-associated-with-severe-clinical-manifestations-in-systemic-lupus-erythematosus-and-reduces-cd3%C3%AE-chain-expression-in-t-cells
#13
Kyeong-Man Hong, Hyun-Kyoung Kim, Seong-Yeol Park, Shiv Poojan, Mi-Kyung Kim, Joohon Sung, Betty P Tsao, Jennifer M Grossman, Ornella J Rullo, Jennifer M P Woo, Deborah K McCurdy, Lisa G Rider, Frederick W Miller, Yeong-Wook Song
OBJECTIVE: The importance of hypomethylation in SLE is well recognized; however, the significance of hypermethylation has not been well characterized. We screened hypermethylated marks in SLE and investigated their possible implications. METHODS: DNA methylation marks were screened in SLE whole-blood DNA by microarray, and two marks (CD3Z and VHL hypermethylations) were confirmed by a methylation single-base extension method in two independent ethnic cohorts consisting of 207 SLE patients and 151 controls...
December 10, 2016: Rheumatology
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
#14
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/27915349/roles-of-1-25-oh-2d3-and-vitamin-d-receptor-in-the-pathogenesis-of-rheumatoid-arthritis-and-systemic-lupus-erythematosus-by-regulating-the-activation-of-cd4-t-cells-and-the-pkc%C3%AE-erk-signaling-pathway
#15
Xiao-Jie He, Yan Ding, Wei Xiang, Xi-Qiang Dang
BACKGROUND/AIMS: The study aims to elucidate the roles of 1,25(OH)2D3 and vitamin D receptor (VDR) in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by regulating the activation of CD4+ T cells and the PKCδ/ERK signaling pathway. METHODS: From January 2013 to December 2015, a total of 130 SLE patients, 137 RA patients and 130 healthy controls were selected in this study. Serum levels of 1,25(OH)2D3 and VDR mRNA expression were detected by ELISA and real-time fluorescence quantitative PCR (RT-qPCR)...
2016: Cellular Physiology and Biochemistry
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
#16
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...
December 13, 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
#17
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
#18
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
#19
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
#20
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
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