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https://www.readbyqxmd.com/read/28654702/stomatin-like-protein-2-deficiency-results-in-impaired-mitochondrial-translation
#1
Panagiotis Mitsopoulos, Orsolya Lapohos, Woranontee Weraarpachai, Hana Antonicka, Yu-Han Chang, Joaquín Madrenas
Mitochondria translate the RNAs for 13 core polypeptides of respiratory chain and ATP synthase complexes that are essential for the assembly and function of these complexes. This process occurs in close proximity to the mitochondrial inner membrane. However, the mechanisms and molecular machinery involved in mitochondrial translation are not fully understood, and defects in this process can result in severe diseases. Stomatin-like protein (SLP)-2 is a mainly mitochondrial protein that forms cardiolipin- and prohibitin-enriched microdomains in the mitochondrial inner membrane that are important for the formation of respiratory supercomplexes and their function...
2017: PloS One
https://www.readbyqxmd.com/read/28654435/myasthenia-gravis-new-developments-in-research-and-treatment
#2
Amelia Evoli
PURPOSE OF REVIEW: Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than as a single disease. This review summarizes recent advances in pathophysiology which confirm the disease heterogeneity, and may help find disease-targeted and patient-targeted therapies. RECENT FINDINGS: Antibodies to the acetylcholine receptor, the muscle-specific tyrosine kinase and the lipoprotein receptor protein 4, characterize disease subtypes with distinct clinical traits and immune-pathogenic mechanisms...
June 24, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28654055/chromatin-immunoprecipitation-chip-in-mouse-t-cell-lines
#3
Benedetto Daniele Giaimo, Francesca Ferrante, Tilman Borggrefe
Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, and nucleosome eviction. Such regulation requires the binding of signal-sensitive transcription factors (TFs) that recruit chromatin-modifying enzymes at regulatory elements defined as enhancers. Understanding how signaling cascades regulate enhancer activity requires a comprehensive analysis of the binding of TFs, chromatin modifying enzymes, and the occupancy of specific histone marks and histone variants...
June 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28653862/optimal-response-to-dimethyl-fumarate-associates-in-ms-with-a-shift-from-an-inflammatory-to-a-tolerogenic-blood-cell-profile
#4
Silvia Medina, Noelia Villarrubia, Susana Sainz de la Maza, José Lifante, Lucienne Costa-Frossard, Ernesto Roldán, Carmen Picón, José C Álvarez-Cermeño, Luisa M Villar
BACKGROUND: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. OBJECTIVE: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. METHODS: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28653572/regulatory-t-cells-as-a-target-in-anticancer-immunotherapy
#5
Tomohiro Enokida, Hiroyoshi Nishikawa
No abstract text is available yet for this article.
June 2017: Immunotherapy
https://www.readbyqxmd.com/read/28652599/regulatory-t-cells-keep-your-hair-on
#6
Shimona Starling
No abstract text is available yet for this article.
June 27, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28652580/immunological-phenotype-of-the-murine-lrba-knockout
#7
Laura Gámez-Díaz, Julika Neumann, Fiona Jäger, Michele Proietti, Felicitas Felber, Pauline Soulas-Sprauel, Lisa Perruzza, Fabio Grassi, Tamara Kögl, Peter Aichele, Manfred Kilimann, Bodo Grimbacher, Sophie Jung
Biallelic mutations in the human Lipopolysaccharide Responsive Beige-like Anchor (LRBA) gene lead to a primary immunodeficiency known as LRBA deficiency, characterized by a broad range of clinical manifestations including autoimmunity, organomegaly, hypogammaglobulinemia and recurrent infections. Considering the phenotypic heterogeneity in patients and the severity of the disease, our aim was to assess the role of LRBA in immune cells and to understand the underlying pathomechanisms through the study of a Lrba knockout (Lrba(-/-)) mouse model...
June 27, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28652577/human-in-vitro-induced-regulatory-t-cells-display-dlgh1dependent-and-pkc-%C3%AE-restrained-suppressive-activity
#8
Alexandra Zanin-Zhorov, Sudha Kumari, Keli L Hippen, Sarah C Merkel, Margaret L MacMillan, Bruce R Blazar, Michael L Dustin
In vitro induced human regulatory T cells (iTregs) have demonstrated in vivo therapeutic utility, but pathways regulating their function have not been elucidated. Here, we report that human iTregs generated in vitro from naïve cord blood cells preferentially recruit Disc large homolog 1 (Dlgh1) and exclude protein kinase C (PKC)-θ from immunological synapses formed on supported lipid bilayers with laterally mobile ICAM-1 and anti-CD3 mAb. Also, iTregs display elevated Dlgh1 overall and Dlgh1-dependent p38 phosphorylation, higher levels of phosphatase and tensin homolog (PTEN), and diminished Akt phosphorylation...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28652399/c-rel-and-i%C3%AE%C2%BAbns-govern-common-and-independent-steps-of-regulatory-t-cell-development-from-novel-cd122-expressing-pre-precursors
#9
Marc Schuster, Carlos Plaza-Sirvent, Anne-Marie Matthies, Ulrike Heise, Andreas Jeron, Dunja Bruder, Alexander Visekruna, Jochen Huehn, Ingo Schmitz
Foxp3-expressing regulatory T cells (Tregs) are essential regulators of immune homeostasis and, thus, are prime targets for therapeutic interventions of diseases such as cancer and autoimmunity. c-REL and IκBNS are important regulators of Foxp3 induction in Treg precursors upon γ-chain cytokine stimulation. In c-REL/IκBNS double-deficient mice, Treg numbers were dramatically reduced, indicating that together, c-REL and IκBNS are pivotal for Treg development. However, despite the highly reduced Treg compartment, double-deficient mice did not develop autoimmunity even when aged to more than 1 y, suggesting that c-REL and IκBNS are required for T cell effector function as well...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652317/the-protein-phosphatase-4-complex-promotes-the-notch-pathway-and-wingless-transcription
#10
Eric T Hall, Tirthadipa Pradhan-Sundd, Faaria Samnani, Esther M Verheyen
The Wnt/Wingless (Wg) pathway controls cell fate specification, tissue differentiation and organ development across organisms. Using an in vivo RNAi screen to identify novel kinase and phosphatase regulators of the Wg pathway, we identified subunits of the serine threonine phosphatase Protein phosphatase 4 (PP4). Knockdown of the catalytic and the regulatory subunits of PP4 cause reductions in the Wg pathway targets Senseless and Distal-less. We find that PP4 regulates the Wg pathway by controlling Notch-driven wg transcription...
June 26, 2017: Biology Open
https://www.readbyqxmd.com/read/28652179/non-coding-rna-regulation-of-t-cell-biology-implications-for-age-associated-cardiovascular-diseases
#11
REVIEW
Jose Coelho-Lima, Ioakim Spyridopoulos
Prevalence of age-associated cardiovascular diseases (CVD) has dramatically increased as a result of improvements in life expectancy. Chronic inflammation is a shared pathophysiological feature of age-associated CVDs, indicating a role for the immune system in the onset and development of CVDs. Indeed, ageing elicits profound changes in both the cardiovascular and immune system, especially in the T cell compartment. Although such changes have been well described at the cellular level, the molecular mechanisms underlying immune-mediated cardiovascular ageing remain largely unexplored...
June 23, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28652108/hidradenitis-suppurativa-is-characterised-by-dysregulation-of-the-th17-treg-cell-axis-which-is-corrected-by-anti-tnf-therapy
#12
Barry Moran, Cheryl M Sweeney, Rosalind Hughes, Anna Malara, Shivashini Kirthi, Anne-Marie Tobin, Brian Kirby, Jean M Fletcher
Hidradenitis suppurativa (HS) is a chronic, inflammatory and debilitating disease of hair follicles with 1-4% prevalence and high morbidity. There is a dearth of information on the pathogenesis and immune dysregulation underlying HS therefore we carried out a detailed analysis of skin infiltrating T cells. Cells isolated from skin biopsies and blood from HS patients and healthy controls were analysed by 16-parameter flow cytometry to provide detailed profiles of CD4 T cell subsets. We observed substantial infiltration of inflammatory T cells with a striking Th17-skewed cytokine profile in HS skin, these cells expressed the Th17 lineage marker CD161 and IL-17, as well as other pro-inflammatory cytokines GM-CSF, IL-22, IFN-γ, and TNF...
June 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28652101/salt-inflammatory-joint-disease-and-autoimmunity
#13
Johanna Sigaux, Luca Semerano, Guillaume Favre, Natacha Bessis, Marie-Christophe Boissier
Salt is a vital nutrient. Excess salt intake, however, has recently been blamed for triggering and/or worsening certain autoimmune diseases. In vitro, the cells involved in innate and adaptive immune responses exhibit an inflammatory profile when placed in hypertonic saline. More specifically, macrophages release increased amounts of proinflammatory cytokines, produce reactive oxygen species, and become capable of activating the inflammasome. T helper cells, via activation of serum and glucocorticoid-regulated kinase 1 (SGK1), overexpress IL-17A and IL-23R and differentiate into Th17 cells; whereas regulatory T cells lose the inhibitory capabilities needed to preserve self-tolerance...
June 23, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28652007/cytokines-affecting-cd4-t-regulatory-cells-in-transplant-tolerance-iii-interleukin-5-il-5-promotes-survival-of-alloantigen-specific-cd4-t-regulatory-cells
#14
Bruce M Hall, Karren M Plain, Giang T Tran, Nirupama D Verma, Catherine M Robinson, Masaru Nomura, Rochelle Boyd, Suzanne J Hodgkinson
CD4(+)T cells mediate antigen-specific allograft tolerance, but die in culture without activated lymphocyte derived cytokines. Supplementation of the media with cytokine rich supernatant, from ConA activated spleen cells, preserves the capacity of tolerant cells to transfer tolerance and suppress rejection. rIL-2 or rIL-4 alone are insufficient to maintain these cells, however. We observed that activation of naïve CD4(+)CD25(+)FOXP3(+)Treg with alloantigen and the Th2 cytokine rIL-4 induces them to express interleukin-5 specific receptor alpha (IL-5Rα) suggesting that IL-5, a Th2 cytokine that is produced later in the immune response may promote tolerance mediating Treg...
June 23, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28651594/the-cd4-t-cell-regulatory-network-mediates-inflammatory-responses-during-acute-hyperinsulinemia-a-simulation-study
#15
Mariana E Martinez-Sanchez, Marcia Hiriart, Elena R Alvarez-Buylla
BACKGROUND: Obesity is frequently linked to insulin resistance, high insulin levels, chronic inflammation, and alterations in the behaviour of CD4+ T cells. Despite the biomedical importance of this condition, the system-level mechanisms that alter CD4+ T cell differentiation and plasticity are not well understood. RESULTS: We model how hyperinsulinemia alters the dynamics of the CD4+ T regulatory network, and this, in turn, modulates cell differentiation and plasticity...
June 26, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28651576/decreased-t-helper-17-cells-in-tuberculosis-is-associated-with-increased-percentages-of-programmed-death-ligand-1-t-helper-2-and-regulatory-t-cells
#16
Chin-Chung Shu, Ming-Fang Wu, Jann-Yuan Wang, Hsin-Chih Lai, Li-Na Lee, Bor-Luen Chiang, Chong-Jen Yu
BACKGROUND: Tuberculosis (TB) is one of the most common infectious diseases worldwide. During active tuberculosis, T helper (Th) 17 cells are decreased, however the association with inhibitory immune regulation is unclear. METHODS: We enrolled 27 patients with TB and 20 age- and sex-matched controls and studies their lymphocyte status. Peripheral blood lymphocytes were isolated and programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) were measured on Th17 cells by using flow cytometry after the cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 6 h...
June 26, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28651365/cathepsin-k-inhibitors-for-osteoporosis-biology-potential-clinical-utility-and-lessons-learned
#17
Matthew T Drake, Bart L Clarke, Merry Jo Oursler, Sundeep Khosla
Cathepsin K is a cysteine protease member of the cathepsin lysosomal protease family. While cathepsin K is highly expressed in osteoclasts, lower levels of cathepsin K are also found in a variety of other tissues. Secretion of cathepsin K from the osteoclast into the sealed osteoclast-bone cell interface results in efficient degradation of type I collagen. The absence of cathepsin K activity in humans results in pycnodysostosis, characterized by increased bone mineral density and fractures. Pharmacological cathepsin K inhibition leads to continuous increases in BMD for up to five years of treatment and improves bone strength at the spine and hip...
June 23, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28651122/activation-of-irf3-contributes-to-ifn-%C3%AE-and-isg54-expression-during-the-immune-responses-to-b16f10-tumor-growth
#18
Zachary Guinn, Deborah M Brown, Thomas M Petro
Interferon Regulatory Factor (IRF-3) has been shown to contribute to immune control of B16 melanoma tumor growth. We have shown previously that IRF-3 has a role in IFN-γ-induced expression of pro-apoptotic interferon stimulated gene 54 (ISG54) in macrophages and IFN-γ in T cells. To investigate the IRF3-IFN-γ-ISG54 nexus, we injected C57Bl/6 (B6) and IRF3KO mice s.c. with luciferase-producing B16-F10 tumor cells. Tumor growth as measured by luciferase levels was similar between B6 and IRF3KO mice at days 2 and 6, but was significantly greater at day 9 in IRF3KO mice compared with B6 mice...
June 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28651073/hemophilia-a-inhibitor-treatment-the-promise-of-engineered-t-cell-therapy
#19
REVIEW
Kalpana Parvathaneni, Maha Abdeladhim, Kathleen P Pratt, David W Scott
Hemophilia A is a bleeding disorder caused by mutations in the gene encoding factor VIII (FVIII), a cofactor protein that is essential for normal blood clotting. Approximately, 1 in 3 patients with severe hemophilia A produce neutralizing antibodies (inhibitors) that block its biologic function in the clotting cascade. Current efforts to eliminate inhibitors consist of repeated FVIII injections under what is termed an "ITI" protocol (Immune Tolerance Induction). However, this method is extremely costly and approximately 30% of patients undergoing ITI do not achieve peripheral tolerance...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28650992/galectin-8-as-an-immunosuppressor-in-experimental-autoimmune-encephalomyelitis-and-a-target-of-human-early-prognostic-antibodies-in-multiple-sclerosis
#20
Evelyn Pardo, Claudia Cárcamo, Reinaldo Uribe-San Martín, Ethel Ciampi, Fabián Segovia-Miranda, Cristobal Curkovic-Peña, Fabián Montecino, Christopher Holmes, Juan Enrique Tichauer, Eric Acuña, Francisco Osorio-Barrios, Marjorie Castro, Priscilla Cortes, Claudia Oyanadel, David M Valenzuela, Rodrigo Pacheco, Rodrigo Naves, Andrea Soza, Alfonso González
Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients...
2017: PloS One
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