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Multiple sclerosis immunology

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https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#1
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
February 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28199198/the-immunological-function-of-gabaergic-system
#2
Chenlu Wu, Xiaobin Qin, Huihui Du, Nengzhang Li, Wenkai Ren, Yuanyi Peng
As a well-known inhibitory neurotransmitter in the central nervous system, gamma-aminobutyric acid also has critical roles in immune system. Immune cells (e.g., lymphocytes, macrophages) express the components of GABAergic system, including GABA receptors, GABA transporters, and GABA metabolic enzymes. The functions of immune cells are highly impacted on GABA signaling. GABAergic components negatively regulate the immune responses, particularly the T cell-mediated immunity, via their effects on production of pro-inflammatory cytokines and activation of signal pathways, like mitogen-activated protein kinase and nuclear factor-kappaB pathways...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28197174/extremely-low-frequency-electromagnetic-fields-stimulation-modulates-autoimmunity-and-immune-responses-a-possible-immuno-modulatory-therapeutic-effect-in-neurodegenerative-diseases
#3
REVIEW
Fabio Guerriero, Giovanni Ricevuti
Increasing evidence shows that extremely low frequency electromagnetic fields (ELF-EMFs) stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELF-EMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28191734/integrative-proteomics-genomics-and-translational-immunology-approaches-reveal-mutated-forms-of-proteolipid-protein-1-plp1-and-mutant-specific-immune-response-in-multiple-sclerosis
#4
Veneta Qendro, Grace A Bugos, Debbie H Lundgren, John Glynn, May H Han, David K Han
In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA...
February 12, 2017: Proteomics
https://www.readbyqxmd.com/read/28188715/-multiple-sclerosis-current-immunological-aspects
#5
Carlos Cuevas-García
Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28169287/il-10-producing-st2-expressing-foxp3-t-cells-in-multiple-sclerosis-brain-lesions
#6
Stephanie Elizabeth Johanna Zandee, Richard Anthony O'Connor, Iris Mair, Melanie Dawn Leech, Anna Williams, Stephen Mark Anderton
CD4(+)Foxp3(+) T regulatory (Treg) cells provide a key defence against inflammatory disease, but also have an ability to produce pro-inflammatory cytokines. The evidence for these two possibilities in multiple sclerosis (MS) is controversial. However, this has largely been based on studies of circulating Treg cells derived from peripheral blood, rather than the central nervous system. We show that Foxp3(+) cells in the brains of MS patients predominantly produce interleukin-10 (IL-10) and show high expression of the IL-33 receptor ST2 (associated with potent Treg function), indicating that Treg in the inflamed brain maintain their suppressive function...
February 7, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28167127/-with-a-little-help-from-my-friends-the-role-of-microbiota-in-thyroid-hormone-metabolism-and-enterohepatic-recycling
#7
Camilla Virili, Marco Centanni
The gut microbiota is composed of over 1200 species of anaerobes and aerobes bacteria along with bacteriophages, viruses and fungal species. Increasing evidence indicates that the intestinal microbiota, beside digestive equilibrium, is also crucial for immunologic, hormonal and metabolic homeostasis. The intestinal microbiota interacts with distant organs by signals which may be part of the bacteria themselves or their metabolites. Dysbiosis has been observed in inflammatory or autoimmune disorders such as multiple sclerosis or type 1 diabetes as well as in obesity and type 2 diabetes...
February 4, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28153503/intake-of-tryptophan-enriched-whey-protein-acutely-enhances-recall-of-positive-loaded-words-in-patients-with-multiple-sclerosis
#8
Cindy K Lieben, Arjan Blokland, Nicolaas E Deutz, Willemijn Jansen, Gang Han, Raymond M Hupperts
BACKGROUND & AIMS: Multiple sclerosis (MS) has physiological and/or immunological characteristics that diminish serotonin metabolism, a neurotransmitter associated with affective and cognitive functions. The aim was examine the acute and dose-dependent effects of a dietary tryptophan (TRP) enrichment on affective and cognitive functions in MS patients. We hypothesized that increased dietary availability of the amino acid TRP enhances serotonin concentrations and improves neuropsychological functions...
January 16, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28151028/the-association-of-interleukin-16-gene-polymorphisms-with-il-16-serum-levels-and-risk-of-multiple-sclerosis
#9
Mehrdad Farrokhi, Aria Masoudifar, Ali Derakhshan, Samira Saadatmand, Hojjat Rouhi-Boroujeni, Masoud Etemadifar, Saeid Rezaei-Zarji, Ameneh Javid, Reza Nobakht, Mitra Deyhimi, Afagh Ekramnia, Milad Ebrahimi, Sajad Sheikh, Sadra Ansaripour, Ali Amani-Beni, Hamidreza Jahanbani-Ardakani
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) that is immunologically mediated in genetically susceptible individuals. Interleukin-16 (IL-16), a pleiotropic cytokine, is an important regulator of T-cell activation which plays a key role in autoimmune diseases. Single-nucleotide polymorphisms (SNPs) in the IL-16 gene may lead to altered cytokine expression or biological activity, and these variations may modulate an individual's risk for MS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28134847/dimethyl-fumarate-therapy-significantly-improves-the-responsiveness-of-t-cells-in-multiple-sclerosis-patients-for-immunoregulation-by-regulatory-t-cells
#10
Janine Schlöder, Carsten Berges, Felix Luessi, Helmut Jonuleit
Multiple sclerosis (MS) is a chronic autoimmune disease caused by an insufficient suppression of autoreactive T lymphocytes. One reason for the lack of immunological control is the reduced responsiveness of T effector cells (Teff) for the suppressive properties of regulatory T cells (Treg), a process termed Treg resistance. Here we investigated whether the disease-modifying therapy of relapsing-remitting MS (RRMS) with dimethyl fumarate (DMF) influences the sensitivity of T cells in the peripheral blood of patients towards Treg-mediated suppression...
January 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28131211/potential-pathophysiological-pathways-that-can-explain-the-positive-effects-of-exercise-on-fatigue-in-multiple-sclerosis-a-scoping-review
#11
REVIEW
Martin Langeskov-Christensen, Etienne J Bisson, Marcia L Finlayson, Ulrik Dalgas
BACKGROUND: Fatigue is one of the most common and most disabling symptoms of multiple sclerosis (MS). It is a multidimensional and complex symptom with multifaceted origins, involving both central and peripheral fatigue mechanisms. Exercise has proven to be safe for people with MS, with cumulating evidence supporting significant reductions in fatigue. However, the potential pathophysiological pathways that can explain the positive effects of exercise on fatigue in MS remain elusive. OBJECTIVES: The objectives were, in PwMS (1) to update the knowledge on the pathophysiology underlying primary and secondary fatigue, and (2) to discuss potential pathophysiological pathways that can explain the positive effects of exercise on MS fatigue...
February 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28130499/amino-acid-catabolism-in-multiple-sclerosis-affects-immune-homeostasis
#12
Laura Negrotto, Jorge Correale
Amino acid catabolism has been implicated in immunoregulatory mechanisms present in several diseases, including autoimmune disorders. Our aims were to assess expression and activity of enzymes involved in Trp and Arg catabolism, as well as to investigate amino acid catabolism effects on the immune system of multiple sclerosis (MS) patients. To this end, 40 MS patients, 30 healthy control subjects, and 30 patients with other inflammatory neurological diseases were studied. Expression and activity of enzymes involved in Trp and Arg catabolism (IDO1, IDO2, Trp 2,3-dioxygenase [TDO], arginase [ARG] 1, ARG2, inducible NO synthetase) were evaluated in PBMCs...
January 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28129686/a-novel-approach-to-discriminate-subgroups-in-multiple-sclerosis
#13
Mehrdad Farrokhi, Zahra Saadatpour, Elyas Fadaee, Leila Saadatpour, Ali Rezaei, Pedram Moeini, Ali Amani Beni
Multiple sclerosis (MS) is an autoimmune disease of central nervous system. Since different types of immune cells are involved in MS pathogenesis, in this study we aimed to evaluate serum levels of several immunological components including soluble CD4 (sCD4), sCD8, sCD163, and immunoglobulins as markers of activity of T-cells, macrophages, and B-cells in different types of MS. Serum levels of sCD4, sCD8, and sCD163 of patients with relapsing-remitting MS (RRMS, n=61), primary progressive MS (PRMS, n=31), secondary progressive MS (SPMS, n=31), clinical isolated syndrome (CIS, n=31) and neuromyelitis optica (NMO, n=31), and healthy controls (n=49) were measured using enzyme-linked immunosorbent assay (ELISA)...
December 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28124759/human-cytomegalovirus-hcmv-ul44-and-ul57-specific-antibody-responses-in-anti-hcmv-positive-patients-with-systemic-sclerosis
#14
Emmanouela Marou, Christos Liaskos, Theodora Simopoulou, Georgios Efthymiou, Efthymios Dardiotis, Christina Katsiari, Thomas Scheper, Wolfgang Meyer, Georgios Hadjigeorgiou, Dimitrios P Bogdanos, Lazaros I Sakkas
The role of human cytomegalovirus (HCMV) has been postulated as a trigger of systemic sclerosis (SSc). The aim of the study was to assess the prevalence of antibodies against HCMV UL44 and UL57 antigens not tested in the past. Sixty SSc patients, 40 multiple sclerosis and 17 normal controls (NCs), all anti-HCMV positive, were tested by immunoblotting. Reactivity to HCMV antigens, expressed as arbitrary units (AUs), was assessed for correlation with clinical and immunological parameters, including types of SSc-related autoantibodies...
January 26, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28117398/tryptophan-2-3-dioxygenase-tdo-deficiency-is-associated-with-subclinical-neuroprotection-in-a-mouse-model-of-multiple-sclerosis
#15
Tobias V Lanz, Sarah K Williams, Aleksandar Stojic, Simeon Iwantscheff, Jana K Sonner, Carl Grabitz, Simon Becker, Laura-Inés Böhler, Soumya R Mohapatra, Felix Sahm, Günter Küblbeck, Toshikazu Nakamura, Hiroshi Funakoshi, Christiane A Opitz, Wolfgang Wick, Ricarda Diem, Michael Platten
The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108364/from-natalizumab-to-fingolimod-in-eight-weeks-immunological-clinical-and-radiological-data-in-quest-of-the-optimal-switch
#16
Andrea Harrer, Georg Pilz, Katrin Oppermann, Marlene Sageder, Shahrzad Afazel, Elisabeth Haschke-Becher, Theo Rispens, Annick de Vries, Mark McCoy, Vlado Stevanovic, Wolfgang Hitzl, Eugen Trinka, Jörg Kraus, Johann Sellner, Peter Wipfler
Natalizumab (NZB) discontinuation during a treatment change is associated with recurrence of disease activity in a significant proportion of multiple sclerosis (MS) patients. The immunological basis why disease reactivation occurs in selected patients is unresolved. In search of a prognostic biomarker for a safe and effective transition from NZB to fingolimod, we monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two drugs in 12 MS patients until six months on fingolimod...
January 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28100077/effects-of-m2000-d-mannuronic-acid-on-learning-memory-retrieval-and-associated-determinants-in-a-rat-model-of-alzheimer-s-disease
#17
Somayeh Athari Nik Azm, Mohammadreza Vafa, Mohammad Sharifzadeh, Majid Safa, Anis Barati, Abbas Mirshafiey
The d-mannuronic acid (M2000) is a novel nonsteroidal anti-inflammatory drug that has immunosuppressive effects together with antioxidant property. M2000 has shown a notable efficacy in experimental models of multiple sclerosis, rheumatoid arthritis, and nephrotic syndrome. In this work, the effect of M2000 on the treatment of Alzheimer's disease (AD) was performed by Morris water maze experiment, and the immunological assessments were carried out by Western blot, apoptosis (procaspase-3, Bax/Bcl2, P53), enzymatic (superoxide dismutase [SOD]), and nonenzymatic oxidative stress (malondialdehyde [MDA]) tests...
February 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28067667/excessive-expression-of-mir-27-impairs-treg-mediated-immunological-tolerance
#18
Leilani O Cruz, Somaye Sadat Hashemifar, Cheng-Jang Wu, Sunglim Cho, Duc T Nguyen, Ling-Li Lin, Aly Azeem Khan, Li-Fan Lu
MicroRNAs (miRs) are tightly regulated in the immune system, and aberrant expression of miRs often results in hematopoietic malignancies and autoimmune diseases. Previously, it was suggested that elevated levels of miR-27 in T cells isolated from patients with multiple sclerosis facilitate disease progression by inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we have demonstrated that, although mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology, these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous manner...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28057805/cns-targeted-autoimmunity-leads-to-increased-influenza-mortality-in-mice
#19
Justin D Glenn, Matthew D Smith, Pei Xue, Yee Chan-Li, Samuel Collins, Peter A Calabresi, Maureen R Horton, Katharine A Whartenby
The discovery that central nervous system (CNS)-targeted autoreactive T cells required a process of licensing in the lung revealed an unexpected relationship between these organs. The clinical and immunological significance of this finding is bidirectional in that it showed not only a mechanism by which T cells become pathogenic before entering the CNS, but also the potential for this process to influence lung immunity as well. Epidemiological studies have shown that people with multiple sclerosis (MS) suffer from increased morbidity and mortality from infectious diseases, independent of immunosuppressive therapies...
February 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28049829/glucocorticoid-receptor-in-t-cells-mediates-protection-from-autoimmunity-in-pregnancy
#20
Jan Broder Engler, Nina Kursawe, María Emilia Solano, Kostas Patas, Sabine Wehrmann, Nina Heckmann, Fred Lühder, Holger M Reichardt, Petra Clara Arck, Stefan M Gold, Manuel A Friese
Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy hormone progesterone to robustly increase Treg frequencies via promiscuous binding to the glucocorticoid receptor (GR) in T cells...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
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