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https://www.readbyqxmd.com/read/29751004/mutations-affecting-the-actin-regulator-wdr1-lead-to-aberrant-lymphoid-immunity
#1
Laurène Pfajfer, Nina K Mair, Raúl Jiménez-Heredia, Ferah Genel, Nesrin Gulez, Ömür Ardeniz, Birgit Hoeger, Sevgi Köstel Bal, Christoph Madritsch, Artem Kalinichenko, Rico Chandra Ardy, Bengü Gerçeker, Javier Rey-Barroso, Hanna Ijspeert, Stuart G Tangye, Ingrid Simonitsch-Klupp, Johannes B Huppa, Mirjam van der Burg, Loïc Dupré, Kaan Boztug
BACKGROUND: The actin-interacting protein WDR1 promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have recently been identified in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells. OBJECTIVE: Given the pleiotropic expression of WDR1, we here investigated to what extent it might control the lymphoid arm of the immune system in humans. METHODS: Histological and detailed immunological analyses were performed to elucidate the role of WDR1 in development and function of B and T lymphocytes...
May 8, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29745443/myricetin-induced-oxidative-stress-suppresses-murine-t-lymphocyte-activation
#2
Javad Ghassemi-Rad, Mahdis Maleki, Allison F Knickle, David W Hoskin
A number of polyphenolic compounds present in fruits and vegetables have the capacity to modulate immune responses; however, the impact of the common plant-derived flavonoid myricetin on T lymphocyte function has not been investigated. We show that myricetin inhibited mouse T lymphocyte activation by bead-immobilized anti-CD3 and anti-CD28 monoclonal antibodies, as indicated by a dose-dependent reduction in cell proliferation and decreased synthesis of interferon-γ, interleukin (IL)-2, IL-4, and IL-17 associated with different T helper cell subsets...
April 16, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29691471/baricitinib-induced-blockade-of-interferon-gamma-receptor-and-interleukin-6-receptor-for-the-prevention-and-treatment-of-graft-versus-host-disease
#3
Jaebok Choi, Matthew L Cooper, Karl Staser, Kidist Ashami, Kiran R Vij, Bing Wang, Lynne Marsala, Jessica Niswonger, Julie Ritchey, Bader Alahmari, Samuel Achilefu, Ikuo Tsunoda, Mark A Schroeder, John F DiPersio
The therapeutic benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are derived from the graft-versus-leukemia (GvL) effects of the procedure. There is a strong association between the GvL effects and graft-versus-host disease (GvHD), a major life-threatening complication of allo-HSCT. The limiting of GvHD while maintaining the GvL effect remains the goal of allo-HSCT. Therefore, identifying optimal therapeutic targets to selectively suppress GvHD while maintaining the GvL effects represents a significant unmet medical need...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29688330/novel-thioglycoside-analogs-of-%C3%AE-galactosylceramide-stimulate-cytotoxicity-and-preferential-th1-cytokine-production-by-human-invariant-natural-killer-t-cells
#4
Ashanty M Melo, Lei Zhang, Éilis F Dockry, Andreea Petrasca, Yasmeen G Ghnewa, Eamon P Breen, Maria E Morrissey, Ciara O'Reilly, Robyn Bruen, Andrew O'Meara, Joanne Lysaght, Xiangming Zhu, Derek G Doherty
Invariant natural killer T (iNKT) cells recognize glycolipid antigens bound to CD1d molecules on antigen-presenting cells. Therapeutic activation of iNKT cells with the xenogeneic glycolipid α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in murine models, but clinical trials using α-GalCer-stimulated human iNKT cells have shown limited efficacy. We synthesized a series of thioglycoside analogs of α-GalCer with different substituents to the galactose residue and found that two of these compounds, XZ7 and XZ11, bound to CD1d-transfected HeLa cells and activated lines of expanded human iNKT cells...
April 6, 2018: Glycobiology
https://www.readbyqxmd.com/read/29626602/protective-properties-of-combined-fungal-polysaccharides-from-cordyceps-sinensis-and-ganoderma-atrum-on-colon-immune-dysfunction
#5
Song-Tao Fan, Shao-Ping Nie, Xiao-Jun Huang, Sunan Wang, Jie-Lun Hu, Jun-Hua Xie, Qi-Xing Nie, Ming-Yong Xie
In vivo an ecological network of polysaccharides utilization by gut microbiota is not only an intense competition but also an impressive cooperation pattern. The present study evaluated the in vivo protective effect of combined fungal polysaccharides (CFP) from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction, induced by 150 mg/kg cyclophosphamide (CP). The results showed that C. sinensis polysaccharides (CSP) significantly promoted microbial-derived butyrate to improve histone h3 acetylation mediating regulatory T (Treg) cell specific Foxp3, as well as significantly restored CP-induced elevation of interleukin (IL)-17 and IL-21...
April 4, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29613792/nutshell-extracts-of-xanthoceras-sorbifolia-a-new-potential-source-of-bioactive-phenolic-compounds-as-natural-antioxidant-and-immunomodulator
#6
Li Zhao, Xing Li, Fei Zhang, Juan-Juan Han, Ting Yang, Ze-Qing Ye, Zhe-Zhi Wang, Yuan Zhang
Nutshell of Xanthoceras sorbifolia, a waste product in the production of edible oil, is rich in health-promoting phenolic acids. However, the individual constituents, bioactivities, and mechanism of action are largely unknown. In this study, 20 phenolic compounds were characterized in nutshell extracts (NE) of X. sorbifolia by GC-MS. Four established in vitro studies showed that NE has significant antioxidant potential. Results in vivo indicated that oral administration of NE effectively ameliorated clinical disease severity of experimental autoimmune encephalomyelitis (EAE) and reduced central nervous system (CNS) inflammation and demyelination...
April 3, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29532885/induction-of-th1-chemokine-secretion-in-dermal-fibroblasts-by-vanadium-pentoxide
#7
P Fallahi, R Foddis, G Elia, F Ragusa, A Patrizio, G Guglielmi, G Frenzilli, S Benvenga, A Cristaudo, A Antonelli, S M Ferrari
Vanadium is a soft, silvery‑grey metal with a number of different oxidation states. The most common commercial form of vanadium is vanadium pentoxide (V2O5). All vanadium compounds are considered toxic. An increase in skin rashes has been observed in certain vanadium workers, including the development of atopic dermatitis. However, to the best of our knowledge, no prior in vivo or in vitro studies have evaluated the effect of vanadium exposure in human dermal fibroblasts. The present study evaluated the effect of V2O5 on proliferation and chemokine secretion in dermal fibroblasts...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29517108/vanadium-pentoxide-induces-the-secretion-of-cxcl9-and-cxcl10-chemokines-in-thyroid-cells
#8
P Fallahi, R Foddis, G Elia, F Ragusa, A Patrizio, S Benvenga, A Cristaudo, A Antonelli, S M Ferrari
Vanadium is a grey metal, existing in different states of oxidation, whose most common form in commercial products is vanadium pentoxide (V2O5). All vanadium compounds have been considered toxic. A carcinogenic role of vanadium on the thyroid has recently been proposed. However no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals after exposure to vanadium. In the present study we evaluate the effect of V2O5 on proliferation, and chemokine secretion in normal thyrocytes...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29476742/celastrol-mediates-th17-and-treg-cell-generation-via-metabolic-signaling
#9
Jiabi Zhang, Juan Shan, Xuelu Chen, Shengfu Li, Dan Long, Youping Li
A T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance is involved in many immune disorders and diseases. Celastrol, a Chinese herbal compound that has anti-inflammatory and immunosuppressive properties, has been indicated to suppress T cell proliferation and Th17 cell induction, while facilitating Forkhead box P3 (Foxp3) expression and Treg cell generation. In this study, we explored the impact and mechanism of celastrol on Th17 cell/induced Treg (iTreg) cell induction. CD4+ CD25- T cells were purified, stimulated with anti-CD3 and anti-CD28 antibodies, and polarized in vitro to generate Th17 or iTreg cells in the presence or absence of celastrol...
March 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29440425/bryostatin-1-alleviates-experimental-multiple-sclerosis
#10
Michael D Kornberg, Matthew D Smith, Hasti Atashi Shirazi, Peter A Calabresi, Solomon H Snyder, Paul M Kim
Multiple sclerosis (MS) is an inflammatory disorder targeting the central nervous system (CNS). The relapsing-remitting phase of MS is largely driven by peripheral activation of autoreactive T-helper (Th) 1 and Th17 lymphocytes. In contrast, compartmentalized inflammation within the CNS, including diffuse activation of innate myeloid cells, characterizes the progressive phase of MS, the most debilitating phase that currently lacks satisfactory treatments. Recently, bryostatin-1 (bryo-1), a naturally occurring, CNS-permeable compound with a favorable safety profile in humans, has been shown to act on antigen-presenting cells to promote differentiation of lymphocytes into Th2 cells, an action that might benefit Th1-driven inflammatory conditions such as MS...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29377154/a-novel-glycocluster-molecule-prevents-timothy-induced-allergic-airway-inflammation-in-mice
#11
M Lehto, H Wolff, R Leino, H Alenius, J Savolainen
BACKGROUND: Allergen-specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th)2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipid A (MPLA) in a grass allergen-induced chronic allergic inflammation model in mice...
January 26, 2018: Allergy
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#12
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29222519/virtual-screening-for-inhibitors-of-the-human-tslp-tslpr-interaction
#13
Dries Van Rompaey, Kenneth Verstraete, Frank Peelman, Savvas N Savvides, Koen Augustyns, Pieter Van Der Veken, Hans De Winter
The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Rα), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP:TSLPR complex to investigate the drugability of this complex...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29188061/effect-of-coriolus-versicolor-glucan-on-the-stimulation-of-cytokine-production-in-sarcoma-180-bearing-mice
#14
Annoor Awadasseid, Kuugbee Eugene, Mayada Jamal, Jie Hou, Ahmed Musa Hago, Yaser Gamallat, Abdo Meyiah, Djibril Bamba, Chiwala Gift, Mohnad Abdalla, Yufang Ma, Yi Xin
Coriolus versicolor (CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and interferon (IFN)-α and -γ, were investigated by ELISA...
December 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29155882/pharmacological-inhibition-of-ror%C3%AE-t-suppresses-the-th17-pathway-and-alleviates-arthritis-in-vivo
#15
Ulf Guendisch, Jessica Weiss, Florence Ecoeur, Julia Christina Riker, Klemens Kaupmann, Joerg Kallen, Samuel Hintermann, David Orain, Janet Dawson, Andreas Billich, Christine Guntermann
Retinoic acid receptor-related-orphan-receptor-C (RORγt) is the key transcription factor that is driving the differentiation of IL-17 producing T-helper 17 (Th17) cells that are implicated in the pathology of various autoimmune and inflammatory diseases. Based on the importance of RORγt in promoting Th17-driven pathology, there is considerable interest to develop low-molecular-weight compounds with the aim of inhibiting the transcriptional activity of this nuclear hormone receptor. In this article, we describe the in vitro and in vivo pharmacology of a potent and selective small-molecular-weight RORγt inverse agonist...
2017: PloS One
https://www.readbyqxmd.com/read/29149822/olive-leaf-extracts-act-as-modulators-of-the-human-immune-response
#16
Thea Magrone, Anna Spagnoletta, Rosaria Salvatore, Manrico Magrone, Francesco Dentamaro, Matteo A Russo, Graziana Difonzo, Carmine Summo, Francesco Caponio, Emilio Jirillo
BACKGROUND: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs. METHODS: Peripheral blood mononuclear cells from twenty-five healthy donors were cultured in the presence of 3 µg of two OLE extracts, extract A (resuspended in water) and extract B (resuspended in 70% ethanol)...
2018: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29123137/high-fraction-brookite-films-from-amorphous-precursors
#17
James E S Haggerty, Laura T Schelhas, Daniil A Kitchaev, John S Mangum, Lauren M Garten, Wenhao Sun, Kevin H Stone, John D Perkins, Michael F Toney, Gerbrand Ceder, David S Ginley, Brian P Gorman, Janet Tate
Structure-specific synthesis processes are of key importance to the growth of polymorphic functional compounds such as TiO2 , where material properties strongly depend on structure as well as chemistry. The robust growth of the brookite polymorph of TiO2 , a promising photocatalyst, has been difficult in both powder and thin-film forms due to the disparity of reported synthesis techniques, their highly specific nature, and lack of mechanistic understanding. In this work, we report the growth of high-fraction (~95%) brookite thin films prepared by annealing amorphous titania precursor films deposited by pulsed laser deposition...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122456/sentinels-of-the-type-2-immune-response
#18
REVIEW
Jakob von Moltke, Marion Pepper
Type 2 immune responses have evolved to sense and respond to large, non-replicating infections or non-microbial noxious compounds in tissues. The development of these responses therefore depends upon highly coordinated and tightly regulated tissue-residing cellular sensors and responders. Multiple exposure to type 2 helper T cell (Th2)-inducing stimuli further enhances both the diversity and potency of the response. This review discusses advances in our understanding of the interacting cellular subsets that comprise both primary and secondary type 2 responses...
February 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29075248/the-exometabolome-of-two-model-strains-of-the-roseobacter-group-a-marketplace-of-microbial-metabolites
#19
Gerrit Wienhausen, Beatriz E Noriega-Ortega, Jutta Niggemann, Thorsten Dittmar, Meinhard Simon
Recent studies applying Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) showed that the exometabolome of marine bacteria is composed of a surprisingly high molecular diversity. To shed more light on how this diversity is generated we examined the exometabolome of two model strains of the Roseobacter group, Phaeobacter inhibens and Dinoroseobacter shibae , grown on glutamate, glucose, acetate or succinate by FT-ICR-MS. We detected 2,767 and 3,354 molecular formulas in the exometabolome of each strain and 67 and 84 matched genome-predicted metabolites of P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29066866/halofuginone-ameliorates-inflammation-in-severe-acute-hepatitis-b-virus-hbv-infected-sd-rats-through-ampk-activation
#20
Weili Zhan, Yanhong Kang, Ning Chen, Chongshan Mao, Yi Kang, Jia Shang
The hepatitis B virus (HBV) has caused acute and chronic liver diseases in ~350 million infected people worldwide. Halofuginone (HF) is a plant alkaloid which has been demonstrated to play a crucial role in immune regulation. Our present study explored the function of HF in the immune response of HBV-infected Sprague Dawley (SD) rats. Plasmid containing pCDNA3.1-HBV1.3 was injected in SD rats for the construction of an acute HBV-infected animal model. Our data showed that HF reduced the high concentrations of serum hepatitis B e-antigen, hepatitis B surface antigen, and HBV DNA induced by HBV infection...
2017: Drug Design, Development and Therapy
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