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https://www.readbyqxmd.com/read/29331869/dietary-naringenin-supplementation-attenuates-experimental-autoimmune-encephalomyelitis-by-modulating-autoimmune-inflammatory-responses-in-mice
#1
Junpeng Wang, Ying Qi, Xinli Niu, Hua Tang, Simin Nikbin Meydani, Dayong Wu
Autoimmune disease is highly prevalent in humans. Since conventional therapies have limited efficacy and often come with significant side effects, nutrition may provide an alternative and complementary approach to improving autoimmune disorders. Naringenin, a flavonoid found in citrus fruits, has been shown to have anti-inflammatory and antioxidant properties. Using the experimental autoimmune encephalomyelitis (EAE), a rodent model of human multiple sclerosis, we determined the effect of dietary naringenin (0...
December 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29321652/innate-ifn-%C3%AE-ameliorates-experimental-autoimmune-encephalomyelitis-and-promotes-myeloid-expansion-and-pdl-1-expression
#2
Madeleine P J White, Gill Webster, Faith Leonard, Anne Camille La Flamme
The innate immune system plays a central role in the immune-mediated pathology of multiple sclerosis, and is a therapeutic target for progressive disease. Recently, it has been demonstrated that MIS416, a novel immunomodulatory microparticle that activates NOD-2 and TLR-9-signaling, has disease-modifying activity in multiple sclerosis models. This activity is dependent on innate IFN-γ; however, the precise immune regulatory mechanisms amplified by MIS416 have not previously been determined. Using the experimental autoimmune encephalomyelitis model, MIS416 treatment was associated with IFN-γ-dependant expansion of Treg number and increased suppressive function; however, these cells did not account for disease reduction...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311129/regulatory-t-cells-from-discovery-to-autoimmunity
#3
Alexandra Kitz, Emily Singer, David Hafler
Multiple sclerosis (MS) is a genetically mediated autoimmune disease of the central nervous system. Allelic variants lead to lower thresholds of T-cell activation resulting in activation of autoreactive T cells. Environmental factors, including, among others, diet, vitamin D, and smoking, in combination with genetic predispositions, play a substantial role in disease development and activation of autoreactive T cells. FoxP3+ regulatory T cells (Tregs) have emerged as central in the control of autoreactive T cells...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29295981/circulating-exosomes-suppress-the-induction-of-regulatory-t-cells-via-let-7i-in-multiple-sclerosis
#4
Kimitoshi Kimura, Hirohiko Hohjoh, Masashi Fukuoka, Wakiro Sato, Shinji Oki, Chiharu Tomi, Hiromi Yamaguchi, Takayuki Kondo, Ryosuke Takahashi, Takashi Yamamura
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system. Foxp3+ regulatory T (Treg) cells are reduced in frequency and dysfunctional in patients with MS, but the underlying mechanisms of this deficiency are unclear. Here, we show that induction of human IFN-γ-IL-17A-Foxp3+CD4+ T cells is inhibited in the presence of circulating exosomes from patients with MS. The exosomal miRNA profile of patients with MS differs from that of healthy controls, and let-7i, which is markedly increased in patients with MS, suppresses induction of Treg cells by targeting insulin like growth factor 1 receptor (IGF1R) and transforming growth factor beta receptor 1 (TGFBR1)...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29274729/gemcitabine-directly-inhibits-effector-cd4-t-cell-activation-and-prevents-experimental-autoimmune-encephalomyelitis
#5
Justin D Glenn, Patrick Xue, Katharine A Whartenby
Pro-inflammatory T cells are critical to the pathogenesis of multiple sclerosis (MS). We investigated the potential for the anti-proliferative, pro-apoptotic drug gemcitabine to affect development of MS-relevant effector TH1, TH17, and Treg cells. Gemcitabine directly suppressed proliferation, activation, and induced apoptosis of all effector subsets in subtype and dose-dependent fashion. This drug also prevented development of disease in the MS model experimental autoimmune encephalomyelitis (EAE) and significantly reduced the abundance of TH1 and TH17 cells...
December 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29238350/differentiation-and-transmigration-of-cd4-t-cells-in-neuroinflammation-and-autoimmunity
#6
REVIEW
Sandip Ashok Sonar, Girdhari Lal
CD4+ T cells play a central role in orchestrating protective immunity and autoimmunity. The activation and differentiation of myelin-reactive CD4+ T cells into effector (Th1 and Th17) and regulatory (Tregs) subsets at the peripheral tissues, and their subsequent transmigration across the blood-brain barrier (BBB) into the central nervous system (CNS) parenchyma are decisive events in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. How the Th1, Th17, and regulatory Tregs transmigrate across the BBB into the CNS and cause CNS inflammation is not clearly understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29203425/tgf%C3%AE-1-transduction-enhances-immunomodulatory-capacity-of-neural-stem-cells-in-experimental-autoimmune-encephalomyelitis
#7
Chong Xie, Xing Li, Xiajun Zhou, Zezhi Li, Yuan Zhang, Li Zhao, Yong Hao, Guang-Xian Zhang, Yangtai Guan
Bone marrow-derived neural stem cells (BM-NSCs) have therapeutic effect on EAE, an animal model of multiple sclerosis. However, the beneficial effect is suboptimal due to the limited immunomodulatory capacity of these cells. In this study, we engineered BM-NSCs with inducible TGFβ1, a potent immunosuppressive cytokine, to enhance their anti-inflammatory capacity. We found that i.v. injected TGFβ1-BM-NSCs more effectively suppressed clinical severity, inflammation and demyelination of the central nervous system of EAE mice...
December 5, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#8
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29202792/the-cc-chemokine-ligand-ccl-1-upregulated-by-the-viral-transactivator-tax-can-be-downregulated-by-minocycline-possible-implications-for-long-term-treatment-of-htlv-1-associated-myelopathy-tropical-spastic-paraparesis
#9
Mineki Saito, Hiroe Sejima, Tadasuke Naito, Hiroshi Ushirogawa, Toshio Matsuzaki, Eiji Matsuura, Yuetsu Tanaka, Tatsufumi Nakamura, Hiroshi Takashima
BACKGROUND: Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/ macrophages and T-lymphocytes, and acts as a potent attractant for Th2 cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that plays a major role in inflammatory processes, we investigated the role of CCL1 in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
December 4, 2017: Virology Journal
https://www.readbyqxmd.com/read/29181000/prenatal-administration-of-betamethasone-causes-changes-in-the-t-cell-receptor-repertoire-influencing-development-of-autoimmunity
#10
Anna Gieras, Christina Gehbauer, David Perna-Barrull, Jan Broder Engler, Ines Diepenbruck, Laura Glau, Simon A Joosse, Nora Kersten, Stefanie Klinge, Hans-Willi Mittrücker, Manuel A Friese, Marta Vives-Pi, Eva Tolosa
Prenatal glucocorticoids are routinely administered to pregnant women at risk of preterm delivery in order to improve survival of the newborn. However, in half of the cases, birth occurs outside the beneficial period for lung development. Glucocorticoids are potent immune modulators and cause apoptotic death of immature T cells, and we have previously shown that prenatal betamethasone treatment at doses eliciting lung maturation induce profound thymocyte apoptosis in the offspring. Here, we asked if there are long-term consequences on the offspring's immunity after this treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163808/cd4-t-cell-specific-b7-h1-selectively-inhibits-proliferation-of-na%C3%A3-ve-t-cells-and-th17-differentiation-in-experimental-autoimmune-encephalomyelitis
#11
Sheng-Jia Shi, Mei-Ling Ding, Li-Juan Wang, Jie-Heng Wu, Dong-Hui Han, Guo-Xu Zheng, Zhang-Yan Guo, Wen-Jin Xi, Wei-Jun Qin, An-Gang Yang, Wei-Hong Wen
It is widely acknowledged that interleukin 17-producing T helper (Th17) cells are critically participant in the pathogenesis of multiple sclerosis. In the current study, we identified that the expression of CD4(+)T cells specific co-inhibitory molecule B7-homologue 1(B7-H1) in spleenocytes and mononuclear cells isolated from brains and spinal cord were positive correlated with Th1 and Th17 cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE). Furthermore, B7-H1 transgenic mice developed milder EAE symptoms and fewer Th17 cells than B7-H1 wild type mice...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163476/induction-of-peripheral-tolerance-in-ongoing-autoimmune-inflammation-requires-interleukin-27-signaling-in-dendritic-cells
#12
Rodolfo Thomé, Jason N Moore, Elisabeth R Mari, Javad Rasouli, Daniel Hwang, Satoshi Yoshimura, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad M Rostami
Peripheral tolerance to autoantigens is induced via suppression of self-reactive lymphocytes, stimulation of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Interleukin (IL)-27 induces tolerogenic DCs and Treg cells; however, it is not known whether IL-27 is important for tolerance induction. We immunized wild-type (WT) and IL-27 receptor (WSX-1) knockout mice with MOG35-55 for induction of experimental autoimmune encephalomyelitis and intravenously (i.v.) injected them with MOG35-55 after onset of disease to induce i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158778/helicobacter-pylori-and-gut-microbiota-in-multiple-sclerosis-versus-alzheimer-s-disease-10-pitfalls-of-microbiome-studies
#13
Ah-Mee Park, Seiichi Omura, Mitsugu Fujita, Fumitaka Sato, Ikuo Tsunoda
Alteration of microbiota has been associated with intestinal, inflammatory, and neurological diseases. Abundance of "good bacteria" such as Bifidobacterium, or their products have been generally believed to be beneficial for any diseases, while "bad bacteria" such as pathogenic Helicobacter pylori are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis (MS) and Alzheimer's disease (AD)...
August 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/29153546/vitamin-d3-supplementation-and-the-il-2-il-2r-pathway-in-multiple-sclerosis-attenuation-of-progressive-disturbances
#14
Linda Rolf, Anne-Hilde Muris, Ruud Theunissen, Raymond Hupperts, Jan Damoiseaux, Joost Smolders
Vitamin D3 upregulates IL-2 receptor alpha (IL2RA, CD25)-expression on CD4(+) T cells in vitro. We investigated effects of 48-weeks vitamin D3 supplements on CD25-expression by CD4(+) T cells of patients with multiple sclerosis (MS). There was no significant difference between the vitamin D3 (n=30) and placebo group (n=23) in IL2RA mRNA-expression by PBMC. Likewise, CD25 cell surface-expression by conventional or regulatory T cells (Treg) did not differ between groups, although Treg CD25-expression and circulating soluble-CD25 levels decreased significantly in the placebo but not vitamin D3-group...
November 10, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29118761/immunological-and-clinical-effect-of-diet-modulation-of-the-gut-microbiome-in-multiple-sclerosis-patients-a-pilot-study
#15
Marina Saresella, Laura Mendozzi, Valentina Rossi, Franca Mazzali, Federica Piancone, Francesca LaRosa, Ivana Marventano, Domenico Caputo, Giovanna E Felis, Mario Clerici
Pathogenesis of autoimmune disorders, including multiple sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10) or a "Western Diet" (WD group; N = 10) for at least 12 months...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29051763/il-12p35-inhibits-neuroinflammation-and-ameliorates-autoimmune-encephalomyelitis
#16
Jin Kyeong Choi, Ivy M Dambuza, Chang He, Cheng-Rong Yu, Anita N Uche, Mary J Mattapallil, Rachel R Caspi, Charles E Egwuagu
Multiple sclerosis (MS) is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE), the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29018225/s1p1-deletion-differentially-affects-th17-and-regulatory-t-cells
#17
Ahmet Eken, Rebekka Duhen, Akhilesh K Singh, Mallory Fry, Jane H Buckner, Mariko Kita, Estelle Bettelli, Mohamed Oukka
Sphingosine-1 phosphate receptor 1 (S1P1) is critical for the egress of T and B cells out of lymphoid organs. Although S1P1 agonist fingolimod is currently used for the treatment of multiple sclerosis (MS) little is known how S1P1 signaling regulates Th17 and Treg cell homeostasis. To study the impact of S1P1 signaling on Th17 and Treg cell biology, we specifically deleted S1P1 in Th17 and Treg cells using IL-17A (Cre) and Foxp3 (Cre) mice, respectively. Deletion of S1P1 in Th17 cells conferred resistance to experimental autoimmune encephalomyelitis (EAE)...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28983300/human-tregs-made-antigen-specific-by-gene-modification-the-power-to-treat-autoimmunity-and-antidrug-antibodies-with-precision
#18
REVIEW
Patrick R Adair, Yong Chan Kim, Ai-Hong Zhang, Jeongheon Yoon, David W Scott
Human regulatory CD4(+) T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28962999/nr4a1-plays-a-crucial-modulatory-role-in-th1-th17-cell-responses-and-cns-autoimmunity
#19
Li-Mei Wang, Yuan Zhang, Xing Li, Ming-Liang Zhang, Lin Zhu, Guang-Xian Zhang, Yu-Ming Xu
Nuclear receptor4 group A1 (Nr4a1), an orphan nuclear receptor, is down-regulated in peripheral blood mononuclear cells (MNCs) of individuals with multiple sclerosis (MS), and Nr4a1 deficiency results in severe experimental autoimmune encephalomyelitis (EAE), an animal model of MS, caused by increased macrophage infiltration into the central nervous system (CNS). However, the role of Nr4a1 in macrophage phenotype and T cell responses remains poorly understood. In the present study we show that macrophages/microglia of Nr4a1(-/-) mice, which exhibited earlier onset and more severe clinical EAE, were polarized to an enhanced type 1 (M1) phenotype and produced higher levels of IL-12 and TNF-α than wild type mice...
September 26, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28946394/bifidobacterium-animalis-in-combination-with-human-origin-of-lactobacillus-plantarum-ameliorate-neuroinflammation-in-experimental-model-of-multiple-sclerosis-by-altering-cd4-t-cell-subset-balance
#20
Zohre Salehipour, Dariush Haghmorad, Mojtaba Sankian, Maryam Rastin, Reza Nosratabadi, Mohammad Mehdi Soltan Dallal, Nafiseh Tabasi, Mahdieh Khazaee, Leila Roozbeh Nasiraii, Mahmoud Mahmoudi
BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Recent reports have shown that probiotics can induce immunomodulatory activity with promising effects in inflammatory diseases. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of Lactobacillus plantarum A7, which comprises human commensal bacteria, and Bifidobacterium animalis, a potential probiotic strain, on alleviation of experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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