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SLE AND T cells

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https://www.readbyqxmd.com/read/29792199/nanoparticle-delivery-of-grape-seed-derived-proanthocyanidins-to-airway-epithelial-cells-dampens-oxidative-stress-and-inflammation
#1
S Castellani, A Trapani, A Spagnoletta, L di Toma, T Magrone, S Di Gioia, D Mandracchia, G Trapani, E Jirillo, M Conese
BACKGROUND: Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins...
May 23, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29785672/aberrant-t-cell-subsets-and-cytokines-expression-profile-in-systemic-lupus-erythematosus
#2
Haiyan Zhou, Bailong Hu, Niwen Huang, Xiangang Mo, Wei Li, Bei Zhang, Bo Wei, Mingzhu Gao, Yiming Wang, Xingde Liu, Joshua Liao
To assess T cell subsets and levels of chemokines and cytokines in patients with SLE and determine their relationships between disease activity and organ involvement. Blood samples from SLE patients (n = 24) and healthy controls (n = 36) were analyzed. Frequency of circulating follicular help T cells (Tfh), central memory T cells (Tcm), effector memory T cells (Tem), and naïve T cell subsets was enumerated and their surface markers expression of inducible T cell co-stimulator (ICOS) and programmed death 1(PD-1) protein was examined by flow cytometry...
May 22, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29777158/mesenchymal-stem-cells-and-t-cells-in-the-formation-of-tertiary-lymphoid-structures-in-lupus-nephritis
#3
S Esmaeil Dorraji, Aud-Malin K Hovd, Premasany Kanapathippillai, Gunnstein Bakland, Gro Østli Eilertsen, Stine L Figenschau, Kristin A Fenton
Tertiary lymphoid structures (TLS) develop in the kidneys of lupus-prone mice and systemic lupus erythematosus (SLE) patients with lupus nephritis (LN). Here we investigated the presence of mesenchymal stem cells (MSCs) in the development of TLS in murine LN, as well as the role of human MSCs as lymphoid tissue organizer (LTo) cells on the activation of CD4+ T cells from three groups of donors including Healthy, SLE and LN patients. Mesenchymal stem like cells were detected within the pelvic wall and TLS in kidneys of lupus-prone mice...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29774664/the-lupus-associated-fc%C3%AE-riib-i232t-polymorphism-results-in-impairment-in-the-negative-selection-of-low-affinity-germinal-center-b-cells-via-c-abl
#4
Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29765617/accelerated-model-of-lupus-autoimmunity-and-vasculopathy-driven-by-toll-like-receptor-7-9-imbalance
#5
Yudong Liu, Nickie L Seto, Carmelo Carmona-Rivera, Mariana J Kaplan
Objectives: Activation of endosomal toll-like receptor (TLR)7 or TLR9 has been proposed as a critical step for the initiation and development of SLE. Traditional spontaneous lupus models normally introduce multiple risk alleles, thereby adding additional confounding factors. In the induced lupus models, the role of TLR9 remains unclear. In the present study, we explored the role of an imbalance between TLR7 and TLR9 pathways in the pathogenesis of lupus and its associated vasculopathy using the imiquimod model in TLR9 KO/B6 background...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29762839/circulating-uca1-is-highly-expressed-in-patients-with-systemic-lupus-erythematosus-and-promotes-the-progression-through-the-akt-pathway
#6
C-R Jiang, T-H Li
OBJECTIVE: To investigate the role of Urothelial Carcinoma Associated 1 (UCA1) during the progression of systemic lupus erythematosus (SLE) and the underlying mechanism. PATIENTS AND METHODS: UCA1 expression in peripheral blood of SLE patients, as well as the expression of protein kinase B (AKT) in the peripheral blood mononuclear cell (PBMC), was detected by qRT-PCR. Expression differences in UCA1 and AKT between different groups were compared by t-test or univariate analysis...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29755456/targeting-regulatory-t-cells-to-treat-patients-with-systemic-lupus-erythematosus
#7
REVIEW
Masayuki Mizui, George C Tsokos
Regulatory T cells (Tregs) are central in integration and maintenance of immune homeostasis. Since breakdown of self-tolerance is a major culprit in the pathogenesis of systemic lupus erythematosus (SLE), restoration of the immune tolerance through the manipulation of Tregs can be exploited to treat patients with SLE. New information has revealed that Tregs besides their role in suppressing the immune response are important in tissue protection and regeneration. Expansion of Tregs with low-dose IL-2 represents an approach to control the autoimmune response...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29745892/peripheral-cd4-cd28null-t-cells-as-predictors-of-damage-in-systemic-lupus-erythematosus-patients
#8
Manuel F Ugarte-Gil, César Sánchez-Zúñiga, Rocio V Gamboa-Cardenas, Madeley Aliaga-Zamudio, Francisco Zevallos, Ana Mosqueira-Riveros, Mariela Medina-Chinchón, Giannina Tineo-Pozo, Claudia Elera-Fitzcarrald, Victor Pimentel-Quiroz, Omar Sarmiento-Velasquez, Cristina Reátegui-Sokolova, Jorge M Cucho-Venegas, José Alfaro-Lozano, Zoila Rodriguez-Bellido, César Pastor-Asurza, Graciela S Alarcón, Risto Perich-Campos
OBJECTIVES: To determine whether the CD4+CD28null T-cells subpopulation predicts the occurrence of damage in SLE. METHODS: This longitudinal study was conducted in consecutive SLE patients seen every six months in our Rheumatology Department since 2012. Patients in whom CD4+CD28null T-cells had been measured and who had at least one subsequent visit were included in the study. Survival analyses (univariable and multivariable Cox-regression models) were performed to determine the risk of overall and domain damage (as per the SLICC Damage Index - SDI) as a function of the frequency of this T-cell subpopulation...
May 8, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29724957/c1q-restrains-autoimmunity-and-viral-infection-by-regulating-cd8-t-cell-metabolism
#9
Guang Sheng Ling, Greg Crawford, Norzawani Buang, Istvan Bartok, Kunyuan Tian, Nicole M Thielens, Isabelle Bally, James A Harker, Philip G Ashton-Rickardt, Sophie Rutschmann, Jessica Strid, Marina Botto
Deficiency of C1q, the initiator of the complement classical pathway, is associated with the development of systemic lupus erythematosus (SLE). Explaining this association in terms of abnormalities in the classical pathway alone remains problematic because C3 deficiency does not predispose to SLE. Here, using a mouse model of SLE, we demonstrate that C1q, but not C3, restrains the response to self-antigens by modulating the mitochondrial metabolism of CD8+ T cells, which can themselves propagate autoimmunity...
May 4, 2018: Science
https://www.readbyqxmd.com/read/29724730/metabolic-pathways-and-immunometabolism-in-rare-kidney-diseases
#10
Peter C Grayson, Sean Eddy, Jaclyn N Taroni, Yaíma L Lightfoot, Laura Mariani, Hemang Parikh, Maja T Lindenmeyer, Wenjun Ju, Casey S Greene, Brad Godfrey, Clemens D Cohen, Jeffrey Krischer, Matthias Kretzler, Peter A Merkel
OBJECTIVES: To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. METHODS: Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups...
May 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29724134/cigarette-smoking-and-the-pathogenesis-of-systemic-lupus-erythematosus
#11
Cameron B Speyer, Karen H Costenbader
Systemic lupus erythematosus (SLE) is a multi-system inflammatory autoimmune disease of incompletely understood etiology. It is thought that environmental exposures "trigger" or accelerate the disease in genetically-predisposed individuals. Areas covered: Substantial epidemiological evidence exists to support the association between cigarette smoking and the risk of incident SLE. Recent evidence points to current smoking as the specific risk factor, with decreasing risk 5 years after smoking cessation, and the greatest risk for disease characterized by the presence of SLE- specific autoantibodies...
May 3, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29720240/integrative-analysis-reveals-cd38-as-a-therapeutic-target-for-plasma-cell-rich-pre-disease-and-established-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#12
Suzanne Cole, Alice Walsh, Xuefeng Yin, Mihir D Wechalekar, Malcolm D Smith, Susanna M Proudman, Douglas J Veale, Ursula Fearon, Costantino Pitzalis, Frances Humby, Michele Bombardieri, Amy Axel, Homer Adams, Christopher Chiu, Michael Sharp, John Alvarez, Ian Anderson, Loui Madakamutil, Sunil Nagpal, Yanxia Guo
BACKGROUND: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29717110/il-21-drives-expansion-and-plasma-cell-differentiation-of-autoreactive-cd11c-hi-t-bet-b-cells-in-sle
#13
Shu Wang, Jingya Wang, Varsha Kumar, Jodi L Karnell, Brian Naiman, Phillip S Gross, Saifur Rahman, Kamelia Zerrouki, Richard Hanna, Christopher Morehouse, Nicholas Holoweckyj, Hao Liu, Zerai Manna, Raphaela Goldbach-Mansky, Sarfaraz Hasni, Richard Siegel, Miguel Sanjuan, Katie Streicher, Michael P Cancro, Roland Kolbeck, Rachel Ettinger
Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chi T-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11chi T-bet+ B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells...
May 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29713015/atherogenic-dyslipidemia-promotes-autoimmune-follicular-helper-t-cell-responses-via-il-27
#14
Heeju Ryu, Hoyong Lim, Garam Choi, Young-Jun Park, Minkyoung Cho, Hyeongjin Na, Chul Won Ahn, Young Chul Kim, Wan-Uk Kim, Sang-Hak Lee, Yeonseok Chung
The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe-/- and Ldlr-/- mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3+ follicular helper T cells (TFH cells). TFH cells isolated from Apoe-/- mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c...
April 30, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29705243/a-kindred-with-mutant-ikaros-and-autoimmunity
#15
Erika Van Nieuwenhove, Josselyn E Garcia-Perez, Christine Helsen, Princess D Rodriguez, Pauline A van Schouwenburg, James Dooley, Susan Schlenner, Mirjam van der Burg, Els Verhoeyen, Rik Gijsbers, Seth Frietze, Hilde Schjerven, Isabelle Meyts, Frank Claessens, Stephanie Humblet-Baron, Carine Wouters, Adrian Liston
IKAROS (encoded by IKZF1) is an important hematopoietic transcription factor critical for early B cell differentiation, with major defects known to lead to low B cell numbers and hypogammaglobulinemia. More perplexing is the link between IKZF1 variants and autoimmunity, including polymorphisms associated with susceptibility to SLE, and recently, rare variants driving monogenic autoimmunity. We identified a novel p.L188V mutation in IKZF1 in the index patient and her father and found this mutation to lead to loss of DNA binding...
April 26, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29704668/cytomegalovirus-aggravates-the-autoimmune-phenomenon-in-systemic-autoimmune-diseases
#16
Essam Mohammed Ahmed Janahi, Shukla Das, Sambit Nath Bhattacharya, Shafiul Haque, Naseem Akhter, Arshad Jawed, Mohd Wahid, Raju Kumar Mandal, Mohtashim Lohani, Mohammed Yahya Areeshi, Vishnampettai G Ramachandran, Shaia Almalki, Sajad Ahmad Dar
BACKGROUND: Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. METHODS: We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines...
April 26, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29700819/circular-rna-expression-profile-and-potential-function-of-hsa_circ_0045272-in-systemic-lupus-erythematosus
#17
Lian-Ju Li, Zhi-Wei Zhu, Wei Zhao, Sha-Sha Tao, Bao-Zhu Li, Shu-Zhen Xu, Jie-Bing Wang, Ming-Yue Zhang, Jun Wu, Rui-Xue Leng, Yin-Guang Fan, Hai-Feng Pan, Dong-Qing Ye
Circular RNAs (circRNAs) represent a class of non-coding RNAs that form covalently closed RNA circles with extensive expression and conservation in mammals. Circular RNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases, but studies of circRNA role in systemic lupus erythematosus (SLE) are lacking. The present study measured the circRNA expression profiles in T cells from patients with SLE and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients...
April 26, 2018: Immunology
https://www.readbyqxmd.com/read/29694256/associations-of-circulating-cxcr3-pd-1-cd4-t-cells-with-disease-activity-of-systemic-lupus-erythematosus
#18
Han Lei, Yang Xue, Yu Yiyun, Wan Weiguo, Lv Ling, Hejian Zou
OBJECTIVES: Which helper CD4+ T cell subset contributes to autoantibodies generation and severity of end-organ involvement in lupus patients remains to be explored. Our research aims to investigate the roles of circulating Tfh (cTfh) cell subsets and corresponding CXCR5- Th cells in lupus patients and their correlation with SLEDAI. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from blood of SLE patients as well as healthy donors. The proportion of Th cell Subsets classified from cell surface markers (CD45RO, CXCR5, CXCR3, CCR6, PD-1, ICOS, and CCR7) is detected by flow cytometry...
April 25, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29684755/impaired-tgf-%C3%AE-signaling-in-patients-with-active-systemic-lupus-erythematosus-is-associated-with-an-overexpression-of-il-22
#19
Raja Rekik, Monia Smiti Khanfir, Thara Larbi, Imen Zamali, Asma Beldi-Ferchiou, Ons Kammoun, Soumaya Marzouki, Saloua Hamzaoui, Skander Mrad, Mohamed Ridha Barbouche, Mohamed Habib Houman, Melika Ben Ahmed
The mechanisms leading to the disruption of self-tolerance in systemic lupus erythematosus (SLE) remain elusive. Herein, we aimed to decipher the molecular basis of the impaired response of mononuclear cells to TGF-β1. The Smad3-pathway was explored on CD3+ lymphocytes in either active or non active SLE patients. An impaired transcription of TGF-β1 target genes was demonstrated in the CD3+ lymphocytes of active SLE patients confirming that the defect involves T cells and pointing to its extrinsic nature. We further demonstrate that the defect did not result from an impaired TGF-βRII expression or Smad2/3 phosphorylation suggesting that the mechanism lies downstream Smad2/3 translocation...
April 20, 2018: Cytokine
https://www.readbyqxmd.com/read/29684636/increased-frequency-of-ccr7-cd4-t-cells-from-patients-with-primary-sj%C3%A3-gren-s-syndrome-an-indicator-of-disease-activity-rather-than-of-damage-severity
#20
Chunling Wu, Pingting Yang, Haina Liu, Weiguo Xiao, Lijuan Zhao
Expression of CCR7 on T cells has been reported to be associated with the lymphocytic migration and infiltration, which is recognized as a vital part of the pathogenesis of Primary Sjögren's syndrome (pSS). Here, we compared the expression of CCR7 on CD4+T cells between pSS patients and control groups, including healthy donors (HD) and patients with systemic lupus erythematosus (SLE) and examined correlations with disease activity and damage severity, which were evaluated by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjogren's Syndrome Disease Damage Index (SSDDI), respectively...
April 20, 2018: Cytokine
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