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Myelin NFAT

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https://www.readbyqxmd.com/read/25630465/nfat1-deficit-and-nfat2-deficit-attenuate-eae-via-different-mechanisms
#1
Lena Dietz, Friederike Frommer, Anna-Lena Vogel, Martin Vaeth, Edgar Serfling, Ari Waisman, Mathias Buttmann, Friederike Berberich-Siebelt
EAE serves as an animal model for multiple sclerosis and is initiated by autoreactive T cells that infiltrate the CNS. Recognition of myelin-associated Ags within the CNS leads to activation of the transcription factor family NFAT. Here, we demonstrate an essential role for NFAT in disease induction, as the combined lack of NFAT1 (NFATc2) and NFAT2 (NFATc1) completely protected mice. Single deficiency of either NFAT1 or NFAT2 ameliorated the course of EAE, and NFAT2 ablation resulted in an obstructed proinflammatory reaction...
May 2015: European Journal of Immunology
https://www.readbyqxmd.com/read/24975323/the-immunomodulator-as101-suppresses-production-of-inflammatory-cytokines-and-ameliorates-the-pathogenesis-of-experimental-autoimmune-encephalomyelitis
#2
Li Xie, Jing Chen, Anthony McMickle, Nadia Awar, Soad Nady, Benjamin Sredni, Paul D Drew, Shiguang Yu
We reported that AS101 (organotellurium compound, trichloro(dioxoethylene-O,O') tellurate) inhibited the differentiation of Th17 cells and reduced the production of IL-17 and GM-CSF. In addition, AS101 promoted the production of IL-2 in activated T cells. Flow cytometric analysis showed that AS101 inhibited Th17 cell proliferation. AS101 blocked the activation of transcriptional factor NFAT, Stat3, and RORγt, and increased activation of Erk1/2, suggesting a mechanism of action of AS101. We further demonstrated that AS101 was effective in amelioration of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis...
August 15, 2014: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/23073893/calcineurin-nuclear-factor-of-activated-t-cells-regulation-of-krox-20-expression-in-schwann-cells-requires-elevation-of-intracellular-cyclic-amp
#3
Maulilio J Kipanyula, Ashwin Woodhoo, Mary Rahman, Donna Payne, Kristján R Jessen, Rhona Mirsky
The transcription factor Krox-20 (Egr2) is a master regulator of Schwann cell myelination. In mice from which calcineurin B had been excised in cells of the neural crest lineage, calcineurin-nuclear factor of activated T cells (NFAT) signaling was required for neuregulin-related Schwann cell myelination (Kao et al. [2009] Immunity 12:359-372). Whether NFAT signaling required simultaneous elevation of intracellular cAMP levels was not explored. In vivo, Krox-20 expression requires continuous axon-Schwann cell signaling that in Schwann cell cultures can be mimicked by elevation of intracellular cAMP...
January 2013: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/20696888/hyperactivation-of-nuclear-factor-of-activated-t-cells-1-nfat1-in-t-cells-attenuates-severity-of-murine-autoimmune-encephalomyelitis
#4
Srimoyee Ghosh, Sergei B Koralov, Irena Stevanovic, Mark S Sundrud, Yoshiteru Sasaki, Klaus Rajewsky, Anjana Rao, Martin R Müller
Nuclear factor of activated T cells (NFAT) proteins are a group of Ca(2+)-regulated transcription factors residing in the cytoplasm of resting cells. Dephosphorylation by calcineurin results in nuclear translocation of NFAT and subsequent expression of target genes; rephosphorylation by kinases, including casein kinase 1 (CK1), restores NFAT to its latent state in the cytoplasm. We engineered a hyperactivable version of NFAT1 with increased affinity for calcineurin and decreased affinity for casein kinase 1...
August 24, 2010: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/19741152/oral-administration-of-1-4-aryl-2-mercaptoimidazole-inhibits-t-cell-proliferation-and-reduces-clinical-severity-in-the-murine-experimental-autoimmune-encephalomyelitis-model
#5
Eun Joo Jung, Minkyu Hur, Young Lim Kim, Ge Hyeong Lee, Jeongmin Kim, Ikyon Kim, Minwoo Lee, Ho-Kyun Han, Mi-Soon Kim, Sejin Hwang, Sungjoo Kim, A Mi Woo, Yeup Yoon, Heon Jin Park, Jonghwa Won
T cells play a pivotal role in the initiation and progression of multiple sclerosis. We have found that 1,4-aryl-2-mercaptoimidazole (KRM-III) inhibited T-cell antigen receptor- and phorbol myristate acetate/ionomycin-induced activation of nuclear factor of activated T cells (NFAT) and T-cell proliferation with an IC(50) of 5 microM. The KRM-III-mediated inhibitory effect was specific for NFAT activation but not for nuclear factor kappaB. Oral administration of 90 mg/kg KRM-III resulted in complete abrogation of anti-CD3 antibody-induced T-cell activation and a 45...
December 2009: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/19179536/calcineurin-nfat-signaling-is-required-for-neuregulin-regulated-schwann-cell-differentiation
#6
Shih-Chu Kao, Hai Wu, Jianming Xie, Ching-Pin Chang, Jeffrey A Ranish, Isabella A Graef, Gerald R Crabtree
Schwann cells develop from multipotent neural crest cells and form myelin sheaths around axons that allow rapid transmission of action potentials. Neuregulin signaling through the ErbB receptor regulates Schwann cell development; however, the downstream pathways are not fully defined. We find that mice lacking calcineurin B1 in the neural crest have defects in Schwann cell differentiation and myelination. Neuregulin addition to Schwann cell precursors initiates an increase in cytoplasmic Ca2+, which activates calcineurin and the downstream transcription factors NFATc3 and c4...
January 30, 2009: Science
https://www.readbyqxmd.com/read/18606704/novel-immunomodulatory-properties-of-berbamine-through-selective-down-regulation-of-stat4-and-action-of-ifn-gamma-in-experimental-autoimmune-encephalomyelitis
#7
Yiping Ren, Limin Lu, Taylor B Guo, Ju Qiu, Yiqing Yang, Ailian Liu, Jingwu Z Zhang
Berbamine (BM) is an herbal compound derived from Berberis vulgaris L commonly used in traditional Chinese medicine. In this study, we show that BM has potent anti-inflammatory properties through novel regulatory mechanisms, leading to reduced encephalitogenic T cell responses and amelioration of experimental autoimmune encephalomyelitis (EAE). The treatment effect of BM was attributable to its selective inhibitory effect on the production and action of IFN-gamma in CD4(+) T cells, which was mediated through altered STAT4 expression in T cells...
July 15, 2008: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/15790681/foxp3-interacts-with-nuclear-factor-of-activated-t-cells-and-nf-kappa-b-to-repress-cytokine-gene-expression-and-effector-functions-of-t-helper-cells
#8
Estelle Bettelli, Maryam Dastrange, Mohamed Oukka
Scurfy mice, which are deficient in a functional Foxp3, exhibit a severe lymphoproliferative disorder and display generalized over-production of cytokines. Here, we show that, among the Foxp transcriptional factor family, which includes Foxp1, Foxp2, and Foxp3, only Foxp3 has the ability to inhibit IL-2, IL-4, and IFN-gamma production by primary T helper cells. We found that Foxp3 physically associates with the Rel family transcription factors, nuclear factor of activated T cells (NFAT) and NF-kappaB, and blocks their ability to induce the endogenous expression of their target genes, including key cytokine genes...
April 5, 2005: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/12902496/recombinant-tcr-ligand-induces-early-tcr-signaling-and-a-unique-pattern-of-downstream-activation
#9
Chunhe Wang, Jeffery L Mooney, Roberto Meza-Romero, Yuan K Chou, Jianya Huan, Arthur A Vandenbark, Halina Offner, Gregory G Burrows
Recombinant TCR ligands (RTLs) consisting of covalently linked alpha(1) and beta(1) domains of MHC class II molecules tethered to specific antigenic peptides represent minimal TCR ligands. In a previous study we reported that the rat RTL201 construct, containing RT1.B MHC class II domains covalently coupled to the encephalitogenic guinea pig myelin basic protein (Gp-MBP(72-89)) peptide, could prevent and treat actively and passively induced experimental autoimmune encephalomyelitis in vivo by selectively inhibiting Gp-MBP(72-89) peptide-specific CD4(+) T cells...
August 15, 2003: Journal of Immunology: Official Journal of the American Association of Immunologists
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