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https://www.readbyqxmd.com/read/27912911/hesperidin-ameliorates-immunological-outcome-and-reduces-neuroinflammation-in-the-mouse-model-of-multiple-sclerosis
#1
Dariush Haghmorad, Mohammad Bagher Mahmoudi, Zohreh Salehipour, Zoleikha Jalayer, Amir Abbas Momtazi Brojeni, Maryam Rastin, Parviz Kokhaei, Mahmoud Mahmoudi
Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation...
November 26, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27882475/the-spatio-temporal-expression-profiles-of-cd4-t-cell-differentiation-and-function-related-genes-during-eae-pathogenesis
#2
Yingying Cai, Hu Shen, Chaoyan Qin, Jinfeng Zhou, Weiming Lai, Juping Pan, Changsheng Du
Multiple sclerosis is a CD4(+) T cell-mediated autoimmune disease of the central nervous system. The unbalance of the cytokines and transcription factors critical for CD4(+) T cell differentiation and function is probably the main reason that causes MS. We detected the mRNA expression changes of key cytokines and transcription factors which are critical for Th1, Th2, Th17, and Treg cell differentiation and function in different tissues during EAE pathogenesis. We fund that each gene not only has its own featured expression changes, but also has interaction with one another, which composes a network of immunity...
November 24, 2016: Inflammation
https://www.readbyqxmd.com/read/27836182/myeloid-dendritic-cells-exhibit-defects-in-activation-and-function-in-patients-with-multiple-sclerosis
#3
Jürgen Haas, Alexander Schwarz, Mirjam Korporal-Kuhnke, Sven Jarius, Brigitte Wildemann
BACKGROUND: Regulatory T cells (Tregs) are functionally defective in patients with multiple sclerosis (MS) and this dysfunction is related to an imbalanced composition of naïve and memory Treg subtypes. Several lines of evidence indicate that these abnormalities might result from a premature decline in thymic-dependent Treg neogenesis. Myeloid dendritic cells (mDCs) critically determine Treg differentiation in the thymus, and thymic stromal lymphopoietin receptor (TSLPR) expressed on mDCs is a key component of the signaling pathways involved in this process...
November 2, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27821578/regulatory-b-cells-induce-formation-of-il-10-expressing-t-cells-in-mice-with-autoimmune-neuroinflammation
#4
Andrea Pennati, Spencer Ng, Yuanqiang Wu, Jordan R Murphy, Jiusheng Deng, Srikant Rangaraju, Seneshaw Asress, Jennifer L Blanchfield, Brian Evavold, Jacques Galipeau
: Although B cells are traditionally known for their role in propagating pro-inflammatory immune responses, their immunosuppressive effects have only begun to be recently appreciated. How these regulatory B cells (Bregs) suppress the immune response remains to be worked out in detail. In this paper we show that Bregs can induce formation of conventional FoxP3(+) regulatory T cells (Tregs), as well as a more recently described CD49b(+)CD223(+) regulatory T cell subset, known as type 1 regulatory T cells (Tr1)...
November 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27797962/melanocortin-1-receptor-activation-is-neuroprotective-in-mouse-models-of-neuroinflammatory-disease
#5
Nadine Mykicki, Alexander M Herrmann, Nicholas Schwab, René Deenen, Tim Sparwasser, Andreas Limmer, Lydia Wachsmuth, Luisa Klotz, Karl Köhrer, Cornelius Faber, Heinz Wiendl, Thomas A Luger, Sven G Meuth, Karin Loser
In inflammation-associated progressive neuroinflammatory disorders, such as multiple sclerosis (MS), inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells cause demyelination and neuronal degeneration. Regulatory T cells (Treg) control the activation and infiltration of autoreactive T cells into the central nervous system (CNS). In MS and experimental autoimmune encephalomyelitis (EAE) in mice, Treg function is impaired. We show that a recently approved drug, Nle(4)-d-Phe(7)-α-melanocyte-stimulating hormone (NDP-MSH), induced functional Treg, resulting in amelioration of EAE progression in mice...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27796368/targeting-non-classical-myelin-epitopes-to-treat-experimental-autoimmune-encephalomyelitis
#6
Xiaohua Wang, Jintao Zhang, David J Baylink, Chih-Huang Li, Douglas M Watts, Yi Xu, Xuezhong Qin, Michael H Walter, Xiaolei Tang
Qa-1 epitopes, the peptides that bind to non-classical major histocompatibility complex Ib Qa-1 molecules and are recognized by Qa-1-restricted CD8(+) regulatory T (Treg) cells, have been identified in pathogenic autoimmune cells that attack myelin sheath in experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis [MS]). Additionally, immunization with such epitopes ameliorates the EAE. However, identification of such epitopes requires knowledge of the pathogenic autoimmune cells which are largely unknown in MS patients...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27792007/single-nucleotide-polymorphisms-in-the-foxp3-gene-are-associated-with-increased-risk-of-relapsing-remitting-multiple-sclerosis
#7
Mohammad Mahdi Eftekharian, Arezou Sayad, Mir Davood Omrani, Masoud Sabouri Ghannad, Rezvan Noroozi, Mehrdokht Mazdeh, Reza Mirfakhraie, Abolfazl Movafagh, Ghodratollah Roshanaei, Tahereh Azimi, Hidetoshi Inoko, Mohammad Taheri
BACKGROUND: Although Multiple Sclerosis (MS) is an autoimmune multifactorial disease with unknown etiology, various genetic and environmental factors are known to contribute to the pathogenesis of the disease. OBJECTIVE: Recent studies have confirmed that the suppressive function of regulatory T cells (T (reg)) is impaired in MS patients and that the FOXP3 gene is a crucial transcription factor in the regulation of CD4+CD25+FOXP3+ Treg cells. Polymorphisms in the promoter region of the FOXP3 gene may alter the gene expression level and, therefore, contribute to the disease susceptibility...
October 21, 2016: Human Antibodies
https://www.readbyqxmd.com/read/27766282/induction-of-gut-regulatory-cd39-t-cells-by-teriflunomide-protects-against-eae
#8
Javier Ochoa-Repáraz, Sara L Colpitts, Christopher Kircher, Eli J Kasper, Kiel M Telesford, Sakhina Begum-Haque, Anudeep Pant, Lloyd H Kasper
OBJECTIVE: To determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally. METHODS: C57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27756335/cerebrospinal-fluid-cytokines-in-lyme-neuroborreliosis
#9
Annukka Pietikäinen, Mikael Maksimow, Tommi Kauko, Saija Hurme, Marko Salmi, Jukka Hytönen
BACKGROUND: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods...
October 18, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27729910/fas-fas-ligand-checkpoint-of-t-cell-functions-in-multiple-sclerosis
#10
Elisabetta Volpe, Manolo Sambucci, Luca Battistini, Giovanna Borsellino
Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27725120/methylene-blue-alleviates-experimental-autoimmune-encephalomyelitis-by-modulating-ampk-sirt1-signaling-pathway-and-th17-treg-immune-response
#11
Jueqiong Wang, Congying Zhao, Peng Kong, Guanyun Bian, Zhe Sun, Yafei Sun, Li Guo, Bin Li
Methylene blue (MB) is an effective neuroprotectant in many neurological disorders. AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1 (SIRT1) plays a crucial role in maintaining inflammatory responses and shows a synergistic effect on cell homeostasis. We investigated the effect of MB on experimental autoimmune encephalomyelitis (EAE), a classical animal model of multiple sclerosis (MS). MB treatment reduced the clinical scores of EAE significantly and attenuated pathological injuries in spinal cords...
October 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27708643/differential-regulation-of-self-reactive-cd4-t-cells-in-cervical-lymph-nodes-and-central-nervous-system-during-viral-encephalomyelitis
#12
Carine Savarin, Cornelia C Bergmann, David R Hinton, Stephen A Stohlman
Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27705922/umbilical-cord-derived-mesenchymal-stem-cells-reversed-the-suppressive-deficiency-of-t-regulatory-cells-from-peripheral-blood-of-patients-with-multiple-sclerosis-in-a-co-culture-a-preliminary-study
#13
Hongna Yang, Jinhua Sun, Feng Wang, Yan Li, Jianzhong Bi, Tingyu Qu
The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs...
September 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27679683/immunomodulation-by-mesenchymal-stem-cells-interplay-between-mesenchymal-stem-cells-and-regulatory-lymphocytes
#14
EDITORIAL
Oscar Ka-Fai Ma, Koon Ho Chan
Mesenchymal stem cells (MSCs) possess immunomodulatory properties, which confer enormous potential for clinical application. Considerable evidence revealed their efficacy on various animal models of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus and uveitis. MSCs elicit their immunomodulatory effects by inhibiting lymphocyte activation and proliferation, forbidding the secretion of proinflammatory cytokines, limiting the function of antigen presenting cells, and inducing regulatory T (Treg) and B (Breg) cells...
September 26, 2016: World Journal of Stem Cells
https://www.readbyqxmd.com/read/27609280/dopaminergic-receptors-and-adrenoceptors-in-circulating-lymphocytes-as-putative-biomarkers-for-the-early-onset-and-progression-of-multiple-sclerosis
#15
Marco Cosentino, Mauro Zaffaroni, Massimiliano Legnaro, Raffaella Bombelli, Laura Schembri, Damiano Baroncini, Anna Bianchi, Raffaella Clerici, Mario Guidotti, Paola Banfi, Giorgio Bono, Franca Marino
Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients...
September 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27605008/sodium-benzoate-a-food-additive-and-a-metabolite-of-cinnamon-enriches-regulatory-t-cells-via-stat6-mediated-upregulation-of-tgf-%C3%AE
#16
Madhuchhanda Kundu, Susanta Mondal, Avik Roy, Jeffrey L Martinson, Kalipada Pahan
Upregulation and/or maintenance of regulatory T cells (Tregs) during autoimmune insults may have therapeutic efficacy in autoimmune diseases. Earlier we have reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders, upregulates Tregs and protects mice from experimental allergic encephalomyelitis, an animal model of multiple sclerosis. However, mechanisms by which NaB increases Tregs are poorly understood. Because TGF-β is an important inducer of Tregs, we examined the effect of NaB on the status of TGF-β...
October 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27602319/upregulation-of-cd4-t-cell-derived-mir-223-in-the-relapsing-phase-of-multiple-sclerosis-patients
#17
Aref Hosseini, Kamran Ghaedi, Somayeh Tanhaei, Mazdak Ganjalikhani-Hakemi, Shohreh Teimuri, Masoud Etemadifar, Mohammad Hossein Nasr Esfahani
OBJECTIVE: MicroRNAs (miRNA) are a class of non-coding RNAs which play key roles in post-transcriptional gene regulation. Previous studies indicate that miRNAs are dysregulated in patients with multiple sclerosis (MS). Th17 and regulatory T (Treg) cells are two subsets of CD4+T-cells which have critical functions in the onset and progression of MS. The current study seeks to distinguish fluctuations in expression of CD4+T-cell derived miR-223 during the relapsing-remitting (RR) phase of MS (RR-MS), as well as the expressions of Th17 and Treg cell markers...
2016: Cell Journal
https://www.readbyqxmd.com/read/27555590/protein-kinase-ck2-governs-the-molecular-decision-between-encephalitogenic-th17-cell-and-treg-cell-development
#18
Alexander Ulges, Esther J Witsch, Gautam Pramanik, Matthias Klein, Katharina Birkner, Ulrike Bühler, Beatrice Wasser, Felix Luessi, Natascha Stergiou, Sarah Dietzen, Till-Julius Brühl, Toszka Bohn, Georg Bündgen, Horst Kunz, Ari Waisman, Hansjörg Schild, Edgar Schmitt, Frauke Zipp, Tobias Bopp
T helper 17 (TH17) cells represent a discrete TH cell subset instrumental in the immune response to extracellular bacteria and fungi. However, TH17 cells are considered to be detrimentally involved in autoimmune diseases like multiple sclerosis (MS). In contrast to TH17 cells, regulatory T (Treg) cells were shown to be pivotal in the maintenance of peripheral tolerance. Thus, the balance between Treg cells and TH17 cells determines the severity of a TH17 cell-driven disease and therefore is a promising target for treating autoimmune diseases...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27536199/mature-dendritic-cells-cause-th17-treg-imbalance-by-secreting-tgf-%C3%AE-1-and-il-6-in-the-pathogenesis-of-experimental-autoimmune-encephalomyelitis
#19
Pingxia Lu, Yingping Cao, Meihua Wang, Peizheng Zheng, Juan Hou, Chanhong Zhu, Jianda Hu
Multiple sclerosis (MS) is generally acknowledged to be an autoimmune disease, but its etiology remains unknown. The most intensively studied animal model of MS is experimental autoimmune encephalomyelitis (EAE). Dendritic cells (DCs), the professional antigen presenting cells (APCs), have gained increasing attention because they connect innate and adaptive immunity. The aim of this study was to determine the role of mature DCs in the pathogenesis of EAE. It was found that the number of mature DCs in the EAE spleen increased compared to the control group (p < 0...
2016: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/27527809/progranulin-a-key-player-in-autoimmune-diseases
#20
Jinlong Jian, Guangfei Li, Aubryanna Hettinghouse, Chuanju Liu
Autoimmune disease encompasses an array of conditions with a variety of presentations and the involvement of multiple organs. Though the etiologies of many autoimmune conditions are unclear, uncontrolled inflammatory immune response is believed to be a major cause of disease development and progression. Progranulin (PGRN), an anti-inflammatory molecule with therapeutic effect in inflammatory arthritis, was identified as an endogenous antagonist of TNFα by competitively binding to TNFR. PGRN exerts its anti-inflammatory activity through multiple pathways, including induction of Treg differentiation and IL-10 expression and inhibition of chemokine release from macrophages...
August 12, 2016: Cytokine
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