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https://www.readbyqxmd.com/read/28421297/suppression-of-th1-differentiation-by-tryptophan-supplementation-in-vivo
#1
Tobias V Lanz, Simon Becker, Soumya R Mohapatra, Christiane A Opitz, Wolfgang Wick, Michael Platten
Metabolism of the essential amino acid tryptophan (trp) is a key endogenous immunosuppressive pathway restricting inflammatory responses. Tryptophan metabolites promote regulatory T cell (Treg) differentiation and suppress proinflammatory T helper cell (Th)1 and Th17 phenotypes. It has been shown that treatment with natural and synthetic tryptophan metabolites can suppress autoimmune neuroinflammation in preclinical animal models. Here, we tested if oral intake of tryptophan would increase immunosuppressive tryptophan metabolites and ameliorate autoimmune neuroinflammation as a safe approach to treat autoimmune disorders like multiple sclerosis (MS)...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28400721/mir-384-regulates-the-th17-treg-ratio-during-experimental-autoimmune-encephalomyelitis-pathogenesis
#2
Xuebin Qu, Jingjing Han, Ying Zhang, Yuanyuan Wang, Jun Zhou, Hongbin Fan, Ruiqin Yao
Specific miRNAs are involved in the pathogenesis of multiple sclerosis (MS), during which IL-17-producing CD4(+) T helper (Th17) cells accumulate in the central nervous system (CNS). In this study, we identified levels of miR-384 as significantly increased in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Over-expression of miR-384 in vivo led to severe EAE, characterized by exacerbated demyelination, and increased inflammatory cell infiltration of the spinal cord; inhibition of miR-384 reversed these changes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28368293/-%C3%AE-caryophyllene-a-cb2-receptor-selective-phytocannabinoid-suppresses-motor-paralysis-and-neuroinflammation-in-a-murine-model-of-multiple-sclerosis
#3
Thaís Barbosa Alberti, Wagner Luiz Ramos Barbosa, José Luiz Fernandes Vieira, Nádia Rezende Barbosa Raposo, Rafael Cypriano Dutra
(-)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain. Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination...
April 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28367355/glyceryl-tribenzoate-a-flavoring-ingredient-inhibits-the-adoptive-transfer-of-experimental-allergic-encephalomyelitis-via-tgf-%C3%AE-implications-for-multiple-sclerosis-therapy
#4
Susanta Mondal, Sridevi Dasarathi, Kalipada Pahan
Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS). Here, we have explored a novel use of glyceryl tribenzoate (GTB), a flavoring ingredient, in ameliorating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS, via TGF-β. Oral feeding of GTB suppressed clinical symptoms of adoptively-transferred relapsing-remitting (RR) EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice...
February 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28363955/dendritic-cells-engineered-to-overexpress-25-hydroxyvitamin-d-1%C3%AE-hydroxylase-and-pulsed-with-a-myelin-antigen-provide-myelin-specific-suppression-of-ongoing-experimental-allergic-encephalomyelitis
#5
Chih-Huang Li, Jintao Zhang, David J Baylink, Xiaohua Wang, Naga Bharani Goparaju, Yi Xu, Samiksha Wasnik, Yanmei Cheng, Edmundo Carreon Berumen, Xuezhong Qin, Kin-Hing William Lau, Xiaolei Tang
Multiple sclerosis (MS) is caused by immune-mediated damage of myelin sheath. Current therapies aim to block such immune responses. However, this blocking is not sufficiently specific and hence compromises immunity, leading to severe side effects. In addition, blocking medications usually provide transient effects and require frequent administration, which further increases the chance to compromise immunity. In this regard, myelin-specific therapy may provide the desired specificity and a long-lasting therapeutic effect by inducing myelin-specific regulatory T (Treg) cells...
March 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#6
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28288125/regulatory-t-cells-promote-myelin-regeneration-in-the-central-nervous-system
#7
Yvonne Dombrowski, Thomas O'Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, George Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard Perbal, Anna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin, Denise C Fitzgerald
Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg...
May 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28283756/dopamine-t-cells-and-multiple-sclerosis-ms
#8
REVIEW
Mia Levite, Franca Marino, Marco Cosentino
Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others...
March 10, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28271325/nebulization-of-rns60-a-physically-modified-saline-attenuates-the-adoptive-transfer-of-experimental-allergic-encephalomyelitis-in-mice-implications-for-multiple-sclerosis-therapy
#9
Susanta Mondal, Suresh B Rangasamy, Supurna Ghosh, Richard L Watson, Kalipada Pahan
Developing a new and effective therapeutic approach against multiple sclerosis (MS) is always an important area of research. RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60, administered through intraperitoneal injection, ameliorated clinical symptoms and disease progression of experimental allergic encephalomyelitis (EAE), an animal model of MS. Since the intravenous route is not preferred for treating a chronic condition, we tested if nebulization of RNS60 could attenuate the disease process of adoptively-transferred EAE in mice...
March 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#10
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#11
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28169287/il-10-producing-st2-expressing-foxp3-t-cells-in-multiple-sclerosis-brain-lesions
#12
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/28157168/regulation-of-t-cell-activation-and-differentiation-by-extracellular-vesicles-and-their-pathogenic-role-in-systemic-lupus-erythematosus-and-multiple-sclerosis
#13
REVIEW
Cristina Ulivieri, Cosima T Baldari
How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs) in the lymph nodes migrate and infiltrate into the target tissues where their reactivation by peripheral tissue antigen is a prerequisite for effector cytokine production and tissue destruction. The target tissue microenvironment, as well as the local microenvironment at the immune synapse formed by T cells that encounter cognate antigen presenting cells (APCs) shave recently emerged as critical factors in shaping the differentiation and function of self-reactive effector T cells, providing the signals required for their activation in the form of the self-antigen and cytokine milieu...
February 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28152213/melatonin-signaling-in-t-cells-functions-and-applications
#14
REVIEW
Wenkai Ren, Gang Liu, Shuai Chen, Jie Yin, Jing Wang, Bie Tan, Guoyao Wu, Fuller W Bazer, Yuanyi Peng, Tiejun Li, Russel J Reiter, Yulong Yin
Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status, and immune function. Importantly, melatonin significantly influences T-cell-mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T-cell biology and the beneficial effects of melatonin in T-cell response-based diseases...
February 2, 2017: Journal of Pineal Research
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
#15
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/28101184/anti-inflammatory-effects-of-luteolin-on-experimental-autoimmune-thyroiditis-in-mice
#16
Nan Xia, Gang Chen, Min Liu, Xiaozhen Ye, Yahui Pan, Jiuyu Ge, Yanting Mao, Hongwei Wang, Jian Wang, Sijing Xie
Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease and is believed to be a predominately T cell-mediated autoimmunity. Signal transducer and activator of transcription (STAT)3 is a crucial transcription factor of T cell-mediated immunity, with key roles in the proliferation and migration of T helper (Th) cells, differentiation of Th cells into Th17 cells, and the balance between Treg cells and Th17 cells. Flavonoid luteolin has been shown to markedly inhibit Tyr705 activation/phosphorylation of STAT3 and exert anti-inflammatory effects in multiple sclerosis...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28067667/excessive-expression-of-mir-27-impairs-treg-mediated-immunological-tolerance
#17
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/28051239/ex-vivo-expansion-of-antigen-specific-cd4-cd25-regulatory-t-cells-from-autologous-na%C3%A3-ve-cd4-t-cells-of-multiple-sclerosis-patients-as-a-potential-therapeutic-approach
#18
Y-J Xiang, M Ren, H Jiang, T-T Yang, Y He, D-H Ao, Y-Y Wang, Q Zhang, X-J He, X-G Gao, G-Z Liu
OBJECTIVE: CD4+CD25+ regulatory T cells (Tregs) have been found to have a decreased effector function in patients with multiple sclerosis (MS). In this study, we co-cultured naïve CD4+ T cells of MS patients with myelin basic protein (MBP)85-99 peptide as specific antigen and allogenic B cells as antigen-presenting cells, in an attempt to generate adequate antigen-specific CD4+CD25+ Tregs with normal or improved immune function. PATIENTS AND METHODS: Naïve CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) from patients with MS (n=5) and healthy controls (HC, n=5)...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28049829/glucocorticoid-receptor-in-t-cells-mediates-protection-from-autoimmunity-in-pregnancy
#19
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
https://www.readbyqxmd.com/read/28038358/il-22-promotes-fas-expression-in-oligodendrocytes-and-inhibits-foxp3-expression-in-t-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway-in-multiple-sclerosis
#20
Jin Zhen, Jun Yuan, Yongwang Fu, Runxiu Zhu, Meiling Wang, Hong Chang, Yan Zhao, Dong Wang, Zuneng Lu
Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4(+)CCR4(+)CCR6(+)CCR10(+) T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells...
December 27, 2016: Molecular Immunology
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