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https://www.readbyqxmd.com/read/28418334/juvenile-idiopathic-arthritis
#1
Kenan Barut, Amra Adrovic, Sezgin Şahin, Özgür Kasapçopur
Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis...
April 5, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28394822/janus-kinase-signal-transducer-and-activator-of-transcription-pathways-in-spondyloarthritis
#2
Smriti K Raychaudhuri, Siba P Raychaudhuri
PURPOSE OF REVIEW: Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway represents a group of several intracellular molecules with a key role in signal pathways activated by growth factors and cytokines. These kinase proteins are associated with the signaling process of multiple key cytokines, which regulates various T-cell subpopulations and their effector cytokines...
April 7, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28392572/an-apoptosis-independent-role-of-trail-in-suppressing-joint-inflammation-and-inhibiting-t-cell-activation-in-inflammatory-arthritis
#3
I-Tsu Chyuan, Hwei-Fang Tsai, Hsiu-Jung Liao, Chien-Sheng Wu, Ping-Ning Hsu
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the regulation of inflammation in rheumatoid arthritis (RA), primarily due to its ability to promote apoptosis in synoviocytes and infiltrating lymphocytes. The aim of this study was to investigate the immunomodulatory mechanism and role of TRAIL in inflammatory arthritis. We created an animal model of inflammatory arthritis and demonstrated that TRAIL significantly inhibited joint inflammation and reduced the severity of arthritis...
April 10, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28373873/novel-senescent-regulatory-t-cell-subset-with-impaired-suppressive-function-in-rheumatoid-arthritis
#4
Johannes Fessler, Andrea Raicht, Rusmir Husic, Anja Ficjan, Christine Schwarz, Christina Duftner, Wolfgang Schwinger, Winfried B Graninger, Martin H Stradner, Christian Dejaco
OBJECTIVE: Premature senescence of lymphocytes is a hallmark of inflammatory rheumatic diseases such as rheumatoid arthritis (RA). Early T-cell aging affects conventional T-cells but is presumably not limited to this cell population; rather it might also occur in the regulatory T-cells (Tregs) compartment. In RA, Tregs fail to halt aberrant immune reactions and disease progression. Whether this is associated with early Treg senescence leading to phenotypic and functional changes of this subset is elusive so far...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28369786/the-role-of-interleukin-6-signalling-and-its-therapeutic-blockage-in-skewing-the-t-cell-balance-in-rheumatoid-arthritis
#5
REVIEW
K Schinnerling, J C Aguillón, D Catalán, L Soto
Therapeutic blockage of cytokine signalling in autoimmune diseases has improved our understanding of the role of these cytokines in triggering, shaping and perpetuating autoimmune responses. In rheumatoid arthritis (RA), immunopathology is driven by a predominance of arthritogenic T helper cells secreting interferon-γ [T helper type 1 (Th1)] and interleukin (IL)-17 (Th17) over regulatory T cells (Treg ). The pleiotropic cytokine IL-6 is crucial to the differentiation of Th17 cells and the balance between pathogenic Th17 and protective Treg ...
April 1, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28364628/human-adipose-tissue-derived-mesenchymal-stem-cells-in-rheumatoid-arthritis-regulatory-effects-on-peripheral-blood-mononuclear-cells-activation
#6
Rasoul Baharlou, Abbas Ahmadi-Vasmehjani, Fatemeh Faraji, Mohammad Reza Atashzar, Mahshid Khoubyari, Salma Ahi, Saiedeh Erfanian, Shadi-Sadat Navabi
BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines...
March 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28362657/epigenetics-of-cd4-t-cells-in-autoimmune-diseases
#7
Zijun Wang, Christopher Chang, Qianjin Lu
PURPOSE OF REVIEW: Autoimmune disorders are a group of overactive symptoms because of abnormal immune responses. Progress of novel mechanisms for autoimmune diseases has been restrained by incomplete understanding of immune disturbance. Recent advances in autoimmune diseases have been well documented by epigenetic alterations (DNA methylation, histone modification, and microRNAs), which alter the transcription activity of genes that are involved in autoimmune responses. RECENT FINDINGS: Multiple environmental factors (trichloroethylene, breast milk, and vitamin C) initiate aberrant epigenetic modifications in CD4 T cells, leading to a list of transcriptional deregulations in several genes (Ifng, Cd70, Tnf, Dnmt3a, and Foxp3) that determine T-cell identity...
March 30, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28358698/increased-numbers-of-cd4-cd25-and-cd8-cd25-t-cells-in-peripheral-blood-of-patients-with-rheumatoid-arthritis-with-parvovirus-b19-infection
#8
Milda Naciute, Gabriele Maciunaite, Diana Mieliauskaite, Rita Rugiene, Aukse Zinkeviciene, Mykolas Mauricas, Modra Murovska, Irute Girkontaite
AIM: To investigate T-cell subpopulations in peripheral blood of human parvovirus B19 DNA-positive (B19(+)) and -negative (B19(-)) patients with rheumatoid arthritis (RA) and healthy persons. PATIENTS AND METHODS: Blood samples were collected from 115 patients with RA and 47 healthy volunteers; 27 patients with RA and nine controls were B19(+) Cluster of differentiation (CD) 4, 8, 25 and 45RA were analyzed on blood cells. CD25 expression on CD4(+)CD45RA(+), CD4(+)CD45RA(-), CD8(+)CD45RA(+), CD8(+)CD45RA(-) subsets were analyzed by flow cytometry...
March 2017: In Vivo
https://www.readbyqxmd.com/read/28349925/paroxetine-alleviates-t-lymphocyte-activation-and-infiltration-to-joints-of-collagen-induced-arthritis
#9
Qingtong Wang, Longsheng Wang, Li Wu, Mei Zhang, Shanshan Hu, Rui Wang, Yongsheng Han, Yujing Wu, Lingling Zhang, Xinming Wang, Wuyi Sun, Wei Wei
T cell infiltration to synovial tissue is an early pathogenic mechanism of rheumatoid arthritis (RA). In the present work, we reveal that G protein coupled receptor kinase 2 (GRK2) is abundantly expressed in T cells of collagen-induced arthritis (CIA). A GRK2 inhibitor, paroxetine protects the joints from inflammation and destruction, primarily through inhibition of both CD4(+) helper T (Th) cell and CD8(+) cytotoxic T (Tc) cell migration to synovial tissue. Meanwhile, paroxetine restores the balance of Th/Tc, effector Th (Theff)/ naïve Th (Thnaive) and effector Tc (Tceff)/ naïve Tc (Tcnaive) to equilibrium by elevating the frequency of Thnaive, Tcnaive and regulatory Th cells; reducing the increased Theff, activated Th and Tceff, having a similar effect as methotrexate (MTX)...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320444/ox40-signaling-is-involved-in-the-autoactivation-of-cd4-cd28-t-cells-and-contributes-to-the-pathogenesis-of-autoimmune-arthritis
#10
Juean Jiang, Cuiping Liu, Mi Liu, Yu Shen, Xiaohan Hu, Qin Wang, Jian Wu, Min Wu, Qi Fang, Xueguang Zhang
BACKGROUND: CD4(+)CD28(-) T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of this study was to investigate the costimulatory effects of OX40 on CD4(+)CD28(-) T cells in autoimmune arthritis...
March 21, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28286938/n-acetyl-l-cysteine-controls-osteoclastogenesis-through-regulating-th17-differentiation-and-rankl-in-rheumatoid-arthritis
#11
Hae-Rim Kim, Kyoung-Woon Kim, Bo-Mi Kim, Kyung-Ann Lee, Sang-Heon Lee
Background/Aims: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). Methods: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes...
March 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28263097/transcriptional-and-epigenetic-regulation-of-follicular-t-helper-cells-and-their-role-in-autoimmunity
#12
Hong Qiu, Haijing Wu, Vera Chan, Chak-Sing Lau, Qianjin Lu
T-follicular helper (Tfh) cells are a specialized subset of T cells that provide help to B cells and promote the formation of germinal centers (GCs). Tfh cells transmit important signals to B cells that drive class switch recombination, somatic hyper-mutation, the generation of high-affinity antibodies, immunological memory and their differentiation into plasma cells or memory B cells in the GCs. Tfh-cell differentiation is regulated by the coordinated functions of distinct cytokines, including interleukin (IL)-6, IL-21, IL-12, IL-23, IL-2, IL-7 and transforming growth factor-β (TGF-β), as well as transcription factors, including B-cell lymphoma 6 protein (Bcl-6), Signal transducers and activators of transcription (STAT)1, STAT3, STAT4, B-cell activating transcription factor (Batf), interferon regulatory factor 4 (IRF4), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (C-Maf), T-cell-specific transcription factor 1 (TCF-1) and Achaete-scute homolog 2 (Acl2), which have been shown to form a complex transcriptional network...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28256939/increased-levels-of-stat1-protein-in-blood-cd4-t-cells-from-systemic-lupus-erythematosus-patients-are-associated-with-perturbed-homeostasis-of-activated-cd45ra-foxp3-hi-regulatory-subset-and-follow-up-disease-severity
#13
Aleš Goropevšek, Maksimiljan Gorenjak, Suzana Gradišnik, Klara Dai, Iztok Holc, Radovan Hojs, Ivan Krajnc, Artur Pahor, Tadej Avčin
In murine systemic lupus erythematosus (SLE), aberrant regulation of interferon (IFN)-alpha-STAT1 signaling and perturbed homeostasis of CD4(+)FOXP3(+) regulatory T cells (Tregs) were described. In the present study, STAT1 signaling and circulating Treg subsets were assessed by flow cytometry in 39 SLE patients and their potential association with disease course was examined during long-term follow-up. Levels of STAT1 protein as measured by median fluorescence intensity (MFI) were significantly increased in SLE CD4 T cells when compared with rheumatoid arthritis patients and healthy controls and were positively correlated with disease activity...
March 3, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28254841/stat5-phosphorylation-in-cd4-t-cells-from-patients-with-sle-is-related-to-changes-in-their-subsets-and-follow-up-disease-severity
#14
Aleš Goropevšek, Maksimiljan Gorenjak, Suzana Gradišnik, Klara Dai, Iztok Holc, Radovan Hojs, Ivan Krajnc, Artur Pahor, Tadej Avčin
Activation of the STAT5 signaling pathway up-regulates antiapoptotic protein Bcl2 and drives proliferation of autoreactive conventional CD4 T cells (Tcons). In systemic lupus erythematosus (SLE), an increased T cell Bcl2 content and perturbed homeostasis of CD45RA(-)FOXP3(hi) activated regulatory T cells (aTregs) were described. We assessed Tcon/Treg subsets and phosphorylation of STAT5 (pSTAT5) in blood T cells from patients with SLE by using conventional and imaging flow cytometry. Forty-one patients with SLE, 33 healthy controls, and 29 patients with rheumatoid arthritis were included...
March 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28216098/potential-influences-of-complement-factor-h-in-autoimmune-inflammatory-and-thrombotic-disorders
#15
Janez Ferluga, Lubna Kouser, Valarmathy Murugaiah, Robert B Sim, Uday Kishore
Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part...
April 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28201972/cell-based-tolerogenic-therapy-experience-from-animal-models-of-multiple-sclerosis-type-1-diabetes-and-rheumatoid-arthritis
#16
Ivana Stojanović, Mirjana Dimitrijević, Marta Vives-Pi, Maria Jose Mansilla, Irma Pujol-Autonell, Silvia Rodríguez-Fernandez, Lenka Palová-Jelínková, David P Funda, Alisa Gruden-Movsesijan, Ljiljana Sofronić-Milosavljević, Catharien M U Hilkens, Eva Martínez-Cáceres, Djordje Miljković
Cell-based tolerogenic therapy is a promising approach for the treatment of autoimmune diseases and transplant rejection. Regulatory T cells and tolerogenic dendritic cells have been particularly explored in the treatment of various autoimmune disorders in experimental models of disease. Although some of these cells have already been tested in a limited number of clinical trials, there is still a need for preclinical research on tolerogenic cells in animal models of autoimmunity. This review will focus on the relevance of data obtained from studies in experimental animal models for the use of tolerogenic cell-based therapy in humans...
February 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28187197/genetic-variants-alter-t-bet-binding-and-gene-expression-in-mucosal-inflammatory-disease
#17
Katrina Soderquest, Arnulf Hertweck, Claudia Giambartolomei, Stephen Henderson, Rami Mohamed, Rimma Goldberg, Esperanza Perucha, Lude Franke, Javier Herrero, Vincent Plagnol, Richard G Jenner, Graham M Lord
The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#18
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28183330/th17-and-cd24-hi-cd27-regulatory-b-lymphocytes-are-biomarkers-of-response-to-biologics-in-rheumatoid-arthritis
#19
Sarah Salomon, Caroline Guignant, Pierre Morel, Gauthier Flahaut, Clément Brault, Clément Gourguechon, Patrice Fardellone, Jean-Pierre Marolleau, Brigitte Gubler, Vincent Goëb
BACKGROUND: The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA). METHODS: This was a non-randomised, single-centre, prospective study. Patients with active RA (American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010) who required the initiation or switch to any biologic drug except rituximab were included...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28169339/dna-methylation-governs-the-dynamic-regulation-of-inflammation-by-apoptotic-cells-during-efferocytosis
#20
Clare A Notley, Christine K Jordan, Jenny L McGovern, Mark A Brown, Michael R Ehrenstein
Efficient clearance of apoptotic cells (AC) is pivotal in preventing autoimmunity and is a potent immunosuppressive stimulus. However, activation of cells prior to apoptosis abolishes their immunoregulatory properties. Here we show using the antigen-induced model of arthritis that the degree of DNA methylation within AC confers their immunomodulatory plasticity. DNA isolated from resting and activated AC mimicked their respective immune effects. Demethylation of DNA abrogated the protective effect of AC whereas remethylation of AC DNA reversed the effects of activation and restored the ability to inhibit inflammation...
February 7, 2017: Scientific Reports
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