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https://www.readbyqxmd.com/read/29775896/dysregulated-network-of-mirnas-involved-in-the-pathogenesis-of-multiple-sclerosis
#1
REVIEW
Sanam Dolati, Faroogh Marofi, Zohreh Babaloo, Leili Aghebati-Maleki, Leila Roshangar, Majid Ahmadi, Reza Rikhtegar, Mehdi Yousefi
Multiple sclerosis (MS) is a chronic and organ-specific autoimmune disease in which immune cells act against the myelin sheath, resulting in central nervous system (CNS) damage. It has been revealed that miRNAs can play significant role in the pathogenesis of MS. These regulatory molecules lead to the activation of different signaling pathways, regulation of several transcriptional factors, influencing the differentiation of Th17 cells, development of Tregs and alteration from Th2 to Th1 response in MS. New studies have discovered that dysregulation of miRNAs may trigger abnormal immune responses leading consequently in the emergence of autoimmunity...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29760692/il17-il17ra-as-a-novel-signaling-axis-driving-mesenchymal-stem-cell-therapeutic-function-in-experimental-autoimmune-encephalomyelitis
#2
Mónica Kurte, Patricia Luz-Crawford, Ana María Vega-Letter, Rafael A Contreras, Gautier Tejedor, Roberto Elizondo-Vega, Luna Martinez-Viola, Catalina Fernández-O'Ryan, Fernando E Figueroa, Christian Jorgensen, Farida Djouad, Flavio Carrión
The therapeutic effect of mesenchymal stem cells (MSCs) in multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755324/effect-of-chronic-oxidative-stress-on-neuroinflammatory-response-mediated-by-cd4-t-cells-in-neurodegenerative-diseases
#3
REVIEW
Helena Solleiro-Villavicencio, Selva Rivas-Arancibia
In a state of oxidative stress, there is an increase of reactive species, which induce an altered intracellular signaling, leading to dysregulation of the inflammatory response. The inability of the antioxidant defense systems to modulate the proinflammatory response is key to the onset and progression of neurodegenerative diseases. The aim of this work is to review the effect of the state of oxidative stress on the loss of regulation of the inflammatory response on the microglia and astrocytes, the induction of different CD4+ T cell populations in neuroinflammation, as well as its role in some neurodegenerative diseases...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29740452/interleukin-27-gene-therapy-prevents-the-development-of-autoimmune-encephalomyelitis-but-fails-to-attenuate-established-inflammation-due-to-the-expansion-of-cd11b-gr-1-myeloid-cells
#4
Jianmin Zhu, Jin-Qing Liu, Zhihao Liu, Lisha Wu, Min Shi, Jianchao Zhang, Jonathan P Davis, Xue-Feng Bai
Interleukin-27 (IL-27) and its subunit P28 (also known as IL-30) have been shown to inhibit autoimmunity and have been suggested as potential immunotherapeutic for autoimmune diseases such as multiple sclerosis (MS). However, the potential of IL-27 and IL-30 as immunotherapeutic, and their mechanisms of action have not been fully understood. In this study, we evaluated the efficacy of adeno-associated viral vector (AAV)-delivered IL-27 (AAV-IL-27) and IL-30 (AAV-IL-30) in a murine model of MS. We found that one single administration of AAV-IL-27, but not AAV-IL-30 completely blocked the development of experimental autoimmune encephalomyelitis (EAE)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29740445/loss-of-perp-in-t-cells-promotes-resistance-to-apoptosis-of-t-helper-17-cells-and-exacerbates-the-development-of-experimental-autoimmune-encephalomyelitis-in-mice
#5
Yan Zhou, Xiao Leng, Yan He, Yan Li, Yuan Liu, Yang Liu, Qiang Zou, Guixiu Shi, Yantang Wang
T helper 17 (Th17) cells are crucial for the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in animals. High frequency of Th17 cells and low sensitivity to activation-induced cell death (AICD) are detected in MS patients. However, the mechanisms underlying apoptosis resistance of T cells remain unclear. Perp is an apoptosis-associated target of p53 and implicated in the development of cancers. Here, we show that loss of Perp in T cells does not affect Th1, Th17, or Treg cell differentiation, but does significantly increase the resistance of Perp -/- Th17 cells to AICD and anti-Fas in Lck-Cre ×  Perp fl/fl mice by inhibiting the caspase-dependent apoptotic pathway...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29720228/characterization-of-a-murine-mixed-neuron-glia-model-and-cellular-responses-to-regulatory-t-cell-derived-factors
#6
Marie Dittmer, Andrew Young, Thomas O'Hagan, George Eleftheriadis, Peter Bankhead, Yvonne Dombrowski, Reinhold J Medina, Denise C Fitzgerald
One of the unmet clinical needs in demyelinating diseases such as Multiple Sclerosis (MS) is to provide therapies that actively enhance the process of myelin regeneration (remyelination) in the central nervous system (CNS). Oligodendrocytes, the myelinating cells of the CNS, play a central role in remyelination and originate from oligodendrocyte progenitor cells (OPCs). We recently showed that depletion of regulatory T cells (Treg) impairs remyelination in vivo, and that Treg-secreted factors directly enhance oligodendrocyte differentiation...
May 2, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29719048/serotonin-decreases-the-production-of-th1-th17-cytokines-and-elevates-the-frequency-of-regulatory-cd4-t-cell-subsets-in-multiple-sclerosis-patients
#7
Priscila M Sacramento, Clarice Monteiro, Aleida S O Dias, Taissa M Kasahara, Thaís B Ferreira, Joana Hygino, Ana Cristina Wing, Regis M Andrade, Fernanda Rueda, Marisa C Sales, Claudia Cristina Vasconcelos, Cleonice A M Bento
Excessive levels of pro-inflammatory cytokines in the central nervous system (CNS) are associated with reduced serotonin (5-HT) synthesis, a neurotransmitter with diverse immune effects. In this study, we evaluated the ability of exogenous 5-HT to modulate the T-cell behavior of patients with multiple sclerosis (MS), a demyelinating autoimmune disease mediated by Th1 and Th17 cytokines. Here, 5-HT attenuated, in vitro, T-cell proliferation and Th1 and Th17 cytokines production in cell cultures from MS patients...
May 2, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29694854/s-nitrosoglutathione-reductase-gsnor-inhibitor-as-an-immune-modulator-in-experimental-autoimmune-encephalomyelitis
#8
Nishant Saxena, Jeseong Won, Seungho Choi, Avtar K Singh, Inderjit Singh
We previously reported that S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, attenuated TH 17-mediated immune responses in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Cellular GSNO homeostasis is regulated via its synthesis by reaction between nitric oxide and glutathione and its enzymatic catabolism by GSNO reductase (GSNOR). In this study, we evaluated potential of reversible inhibitor of GSNOR (N6022) in comparison with exogenous GSNO in immunopathogenesis of EAE...
April 22, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29656444/predicting-therapeutic-response-to-fingolimod-treatment-in-multiple-sclerosis-patients
#9
Bibiana Quirant-Sánchez, José V Hervás-García, Aina Teniente-Serra, Luis Brieva, Ester Moral-Torres, Antonio Cano, Elvira Munteis, María J Mansilla, Silvia Presas-Rodriguez, Juan Navarro-Barriuso, Cristina Ramo-Tello, Eva M Martínez-Cáceres
AIMS: Fingolimod, an orally active immunomodulatory drug for relapsing-remitting multiple sclerosis (RRMS), sequesters T cells in lymph nodes through functional antagonism of the sphingosine-1-phosphate receptor, reducing the number of potential autoreactive cells that migrate to the central nervous system. However, not all RRMS patients respond to this therapy. Our aim was to test the hypothesis that by immune-monitoring RRMS patient's leukocyte subpopulations it is possible to find biomarkers associated with clinical response to fingolimod...
April 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29625181/hyaluronan-in-immune-dysregulation-and-autoimmune-diseases
#10
REVIEW
Nadine Nagy, Hedwich F Kuipers, Payton L Marshall, Esther Wang, Gernot Kaber, Paul L Bollyky
The tissue microenvironment contributes to local immunity and to the pathogenesis of autoimmune diseases - a diverse set of conditions characterized by sterile inflammation, immunity against self-antigens, and destruction of tissues. However, the specific factors within the tissue microenvironment that contribute to local immune dysregulation in autoimmunity are poorly understood. One particular tissue component implicated in multiple autoimmune diseases is hyaluronan (HA), an extracellular matrix (ECM) polymer...
April 3, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29623002/the-role-for-exosomal-micrornas-in-disruption-of-regulatory-t-cell-homeostasis-in-multiple-sclerosis
#11
Kimitoshi Kimura, Hirohiko Hohjoh, Takashi Yamamura
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which myelin and oligodendrocytes are the main targets recognized by inflammatory CD4+ T cells reactive to myelin peptides. Regulatory CD4+ T (Treg) cells normally keep homeostasis of the immune system by inhibiting detrimental effects of inflammatory T cells. However, Treg cells are reduced in patients with MS for unknown reason. This commentary highlights a novel function of circulating exosomes to inhibit the differentiation of Treg cells in MS...
2018: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/29598831/smoking-under-hypoxic-conditions-a-potent-environmental-risk-factor-for-inflammatory-and-autoimmune-diseases
#12
REVIEW
Md Saddam Hussain, Vishwas Tripathi
Autoimmune disease management presents a significant challenge to medical science. Environmental factors potentially increase the risk of developing inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and lupus. Among various environmental stresses, cigarette smoke and hypoxia have both been reported to lead to an enhanced risk of inflammatory and autoimmune diseases.In this review, we shed light on all reported mechanisms whereby cigarette smoke and a hypoxic environment can induce inflammatory and autoimmune diseases and discuss how hypoxic conditions influence the cigarette smoke-induced threat of inflammatory and autoimmune disease development...
March 30, 2018: Military Medical Research
https://www.readbyqxmd.com/read/29593729/genomic-effects-of-the-vitamin-d-receptor-potentially-the-link-between-vitamin-d-immune-cells-and-multiple-sclerosis
#13
REVIEW
Ming Lu, Bruce V Taylor, Heinrich Körner
Vitamin D has a plethora of functions that are important for the maintenance of general health and in particular, the functional integrity of the immune system, such as promoting an anti-inflammatory cytokine profile and reducing the Treg/Th17 ratio. Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative central nervous system (CNS) disorder of probable autoimmune origin. MS is characterized by recurring or progressive demyelination and degeneration of the CNS due in part to a misguided immune response to as yet undefined (CNS) antigens, potentially including myelin basic protein and proteolipid protein...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29593720/the-soluble-form-of-toll-like-receptor-2-is-elevated-in-serum-of-multiple-sclerosis-patients-a-novel-potential-disease-biomarker
#14
Md Jakir Hossain, Elena Morandi, Radu Tanasescu, Nanci Frakich, Marzia Caldano, David Onion, Tola A Faraj, Clett Erridge, Bruno Gran
Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. It was previously shown that toll-like receptor (TLR)-2 signaling plays a key role in the murine experimental autoimmune encephalomyelitis (EAE) model of MS, and that TLR2-stimulation of regulatory T cells (Tregs) promotes their conversion to T helper 17 (Th17) cells. Here, we sought potential sources of TLR2 stimulation and evidence of TLR2 activity in MS patient clinical samples. Soluble TLR2 (sTLR2) was found to be significantly elevated in sera of MS patients ( n  = 21), in both relapse and remission, compared to healthy controls (HC) ( n  = 24)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29589548/characterization-of-regulatory-t-cells-in-multiple-sclerosis-patients-treated-with-interferon-beta-1a
#15
Mohsen Ebrahimi, Ali Ganji, Sarah Zahedi, Parisa Nourbakhsh, Keyvan Ghasami, Ghasem Mosayebi
BACKGROUND: Regulatory T-Cells (Treg Cells), as one of the immune system components, have been highly effective in the autoimmune diseases prevention, particularly multiple sclerosis (MS). Cytokine-based therapies such as interferon beta-1a (IFN-β1a) is a common drug in MS treatment; however, its exact mechanisms are insufficiently described. OBJECTIVE: Therefore, the goal of this study was to evaluate the in vivo impact of IFN-β1a on the Treg Cells in MS. METHODS: In this case-control study, Treg Cells were analysed by flowcytometry in IFN-β1a-treated relapsing-remitting MS (RRMS) in comparison with new cases of MS and healthy subjects...
March 27, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29575350/regulatory-t-cells-in-autoimmune-skin-diseases
#16
Hideyuki Ujiie
CD4+ Foxp3+ regulatory T cells (Tregs) are suppressors of immune activation and play a crucial role in the maintenance of peripheral tolerance. Mutations of Foxp3 result in fatal autoimmunity in multiple organs, including the skin, in both humans and mice. Many studies have demonstrated the altered frequency and functions of Tregs, changes in cytokine and chemokine levels related to Tregs, and the differences in genetic background regarding Tregs in autoimmune skin disorders. Recent studies have extended our knowledge of certain properties of Tregs, especially skin-resident Tregs...
March 25, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29572810/chloroquine-treated-dendritic-cells-require-stat1-signaling-for-their-tolerogenic-activity
#17
Rodolfo Thome, Amanda Pires Bonfanti, Javad Rasouli, Elisabeth Rose Mari, Guang-Xian Zhang, Abdolmohamad Rostami, Liana Verinaud
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are T cell-driven autoimmune diseases of the central nervous system (CNS) where interleukin (IL)-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic dendritic cells (DCs) induce regulatory T (Treg) cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms. Here we show that signal transducer and activator of transcription (STAT) 1 is necessary for CQ-induced tolerogenic DCs (tolDCs) to efficiently suppress EAE...
March 23, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29551498/analysis-of-the-expression-of-mir-34a-mir-199a-mir-30c-and-mir-19a-in-peripheral-blood-cd4-t-lymphocytes-of-relapsing-remitting-multiple-sclerosis-patients
#18
Nooshin Ghadiri, Negaralsadat Emamnia, Mazdak Ganjalikhani-Hakemi, Kamran Ghaedi, Masoud Etemadifar, Mansoor Salehi, Hedayatollah Shirzad, Mohammad Hossein Nasr-Esfahani
BACKGROUND: Multiple sclerosis is an immune-mediated inflammatory disease of central nervous system. MicroRNAs play important roles in autoimmune diseases such as MS. OBJECTIVES: The aim was to evaluate the expression pattern of miR-34a, miR-199a, miR-30c and miR-19a in peripheral blood derived CD4+ T lymphocytes of both relapsing and remitting phases of MS. METHODS: Blood samples from 40 RRMS patients (20 in relapsing and 20 in remitting phase) and 20 healthy volunteers were taken...
March 15, 2018: Gene
https://www.readbyqxmd.com/read/29536745/astaxanthin-effectiveness-in-preventing-multiple-sclerosis-in-animal-model
#19
S Bidaran, A R Ahmadi, P Yaghmaei, M H Sanati, A Ebrahim-Habibi
OBJECTIVE: The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS). BACKGROUND: Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers. METHODS: The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG)...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29535709/a-context-dependent-role-for-%C3%AE-v-integrins-in-regulatory-t-cell-accumulation-at-sites-of-inflammation
#20
Iris Mair, Stephanie E J Zandee, Iqbal S Toor, Louise Saul, Rhoanne C McPherson, Melanie D Leech, Danielle J Smyth, Richard A O'Connor, Neil C Henderson, Stephen M Anderton
Several inflammatory diseases including multiple sclerosis and inflammatory bowel disease have been associated with dysfunctional and/or reduced numbers of Foxp3+ regulatory T cells (Treg). While numerous mechanisms of action have been discovered by which Treg can exert their function, disease-specific Treg requirements remain largely unknown. We found that the integrin αv, which can pair with several β subunits including β8, is highly upregulated in Treg at sites of inflammation. Using mice that lacked αv expression or β8 expression specifically in Treg, we demonstrate that there was no deficit in Treg accumulation in the central nervous system during experimental autoimmune encephalomyelitis and no difference in the resolution of disease compared to control mice...
2018: Frontiers in Immunology
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