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https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#1
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27900387/a-modification-specific-peptide-based-immunization-approach-using-crm197-carrier-protein-development-of-a-selective-vaccine-against-pyroglutamate-a%C3%AE-peptides
#2
Valérie Vingtdeux, Haitian Zhao, Pallavi Chandakkar, Christopher M Acker, Peter Davies, Philippe Marambaud
Strategies aimed at reducing cerebral accumulation of the amyloid-β (Aβ) peptides have therapeutic potential in Alzheimer's disease (AD). Aβ immunization has proven to be effective at promoting Aβ clearance in animal models but adverse effects have hampered its clinical evaluation. The first anti-Aβ immunization clinical trial, which assessed a full-length Aβ1-42 vaccine, increased the risk of encephalitis most likely because of autoimmune pro-inflammatory T helper 1 (Th1) response against all forms of Aβ...
November 28, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27895398/dysregulation-of-innate-immunity-in-ulcerative-colitis-patients-who-fail-anti-tumor-necrosis-factor-therapy
#3
Angela C Baird, Dominic Mallon, Graham Radford-Smith, Julien Boyer, Thierry Piche, Susan L Prescott, Ian C Lawrance, Meri K Tulic
AIM: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n = 12) and compared to healthy controls (n = 12)...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27889082/nod2-promotes-cell-proliferation-and-inflammatory-response-by-mediating-expression-of-tslp-in-human-airway-smooth-muscle-cells
#4
Gaoshun Ni, Yang Chen, Fengqin Wu, Pengxian Zhu, Liqiang Song
The newly discovered intracytosolic pattern recognition receptor nucleotide-binding oligomerization domain 2 (NOD2) has been studied as an important indicator of T helper 2 (Th2) inflammation, and its effect on regulatory T (Treg) cells is likely to modulate the immune response. In this study, we attempted to study the expression of NOD2 and its impact in human airway smooth muscle cells (HASMC). Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of NOD2 in HASMC and comparisons were made between those from asthmatic and non-asthmatic donors; we found that NOD2 was significantly upregulated in asthma patient tissues and cell lines...
November 17, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27876552/long-term-altered-immune-responses-following-fetal-priming-in-a-non-human-primate-model-of-maternal-immune-activation
#5
Destanie R Rose, Milo Careaga, Judy Van de Water, Kim McAllister, Melissa D Bauman, Paul Ashwood
Infection during pregnancy can lead to activation of the maternal immune system and has been associated with an increased risk of having an offspring later diagnosed with a neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD) or Schizophrenia (SZ). Most maternal immune activation (MIA) studies to date have been in rodents and usually involve the use of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). However, since NDD are based on behavioral changes, a model of MIA in non-human primates could potentially provide data that helps illuminate complex behavioral and immune outputs in human NDD...
November 19, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27870664/targeting-il-25-as-a-novel-therapy-in-chronic-rhinosinusitis-with-nasal-polyps
#6
Mingyu Lee, Dae Woo Kim, Hyun-Woo Shin
PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a heterogeneous inflammatory disorder with a poorly understood pathophysiology. Recent findings show that epithelial-derived cytokines, including thymic stromal lymphopoietin, IL-33, and IL-25, can exacerbate Th2 immune responses, ultimately leading to recalcitrant chronic rhinosinusitis and nasal polyp. Although IL-25 is increased in CRSwNP, the targeting of IL-25 as a therapeutic strategy remains largely unexplored...
November 18, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27866769/modular-virus-like-particles-for-sublingual-vaccination-against-group-a-streptococcus
#7
Arjun Seth, Il Gyu Kong, Su-Hyun Lee, Jin-Young Yang, Yong-Soo Lee, Yeji Kim, Nani Wibowo, Anton P J Middelberg, Linda H L Lua, Mi-Na Kweon
Infection with Group A streptococcus (GAS)-an oropharyngeal pathogen-leads to mortality and morbidity, primarily among developing countries and indigenous populations in developed countries. The development of safe and affordable GAS vaccines is challenging, due to the presence of various unique GAS serotypes, antigenic variation within the same serotype, and potential auto-immune responses. In the present study, we evaluated the use of a sublingual freeze-dried (FD) formulation based on immunogenic modular virus-like particles (VLPs) carrying the J8 peptide (J8-VLPs) as a potential safe and cost-effective GAS vaccine for inducing protective systemic and mucosal immunity...
December 12, 2016: Vaccine
https://www.readbyqxmd.com/read/27861815/intestinal-helminth-infection-induces-highly-functional-resident-memory-cd4-t-cells-in-mice
#8
Svenja Steinfelder, Sebastian Rausch, Dörte Michael, Anja A Kühl, Susanne Hartmann
Immunity to intestinal nematodes requires CD4⁺ Th2-cell responses, including IL-4 and IL-13 production. Chronic infection with intestinal nematodes leads to downregulation of these responses, and few functional T helper (Th) 2 cells are detected in secondary lymphoid organs in the chronic phase or after abrogation of infection. Here, we show with a natural murine infection with Heligmosomoides polygyrus that highly functional memory Th2 cells persist in the lamina propria and in addition in the peritoneal cavity (PC) after abrogation of infection...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27855702/tumor-immune-microenvironment-characterization-in-clear-cell-renal-cell-carcinoma-identifies-prognostic-and-immunotherapeutically-relevant-messenger-rna-signatures
#9
Yasin Şenbabaoğlu, Ron S Gejman, Andrew G Winer, Ming Liu, Eliezer M Van Allen, Guillermo de Velasco, Diana Miao, Irina Ostrovnaya, Esther Drill, Augustin Luna, Nils Weinhold, William Lee, Brandon J Manley, Danny N Khalil, Samuel D Kaffenberger, Yingbei Chen, Ludmila Danilova, Martin H Voss, Jonathan A Coleman, Paul Russo, Victor E Reuter, Timothy A Chan, Emily H Cheng, David A Scheinberg, Ming O Li, Toni K Choueiri, James J Hsieh, Chris Sander, A Ari Hakimi
BACKGROUND: Tumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types. RESULTS: We compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores...
November 17, 2016: Genome Biology
https://www.readbyqxmd.com/read/27842944/the-influence-of-hydro-ethanolic-extract-of-portulaca-oleracea-l-on-th1-th2-balance-in-isolated-human-lymphocytes
#10
Vahid Reza Askari, Seyed Abdolrahim Rezaee, Khalil Abnous, Mehrdad Iranshahi, Mohammad Hossein Boskabady
ETHNOPHARMACOLOGICAL RELEVANCE: The anti-inflammatory and anti-oxidants activity of Portulaca oleracea L. (P. oleracea) were mentioned in traditional texts. In previous studies, different anti-inflammatory and anti-oxidant effects of P. oleracea were demonstrated. However, the mechanism of action and immunomodulatory property of this plant are greatly unknown. In the present study, the effect of the extract of this plant on IL-4, IL10, IFN-γ and T helper (h)1/Th2 balance in non-stimulated and stimulated human lymphocytes was examined...
November 10, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27836376/-new-drugs-for-severe-asthma
#11
Caroline Sattler, Roxane Malrin, Gilles Garcia, Marc Humbert
Asthma is a very frequent disease with complex and heterogenous immunological and clinical features. Daily inhaled steroids are the cornerstone of the current therapeutics sometimes associated with long-acting β2-agonist. This controller treatment is effective and allows to control asthma symptoms for the vast majority of the patients. Severe asthma is characterized by a poor level of control of symptoms, with recurrent exacerbations or a chronic airflow limitation despite an optimal management. Severe asthma remains a difficult diagnosis but we have now studies proving the clinical efficacy or promising data about monoclonal antibodies targeting IgE, IL-5, IL-4 or IL-13...
November 8, 2016: La Presse Médicale
https://www.readbyqxmd.com/read/27833589/systemic-approach-to-virulence-gene-network-analysis-for-gaining-new-insight-into-cryptococcal-virulence
#12
Antoni N Malachowski, Mohamed Yosri, Goun Park, Yong-Sun Bahn, Yongqun He, Michal A Olszewski
Cryptococcus neoformans is pathogenic yeast, responsible for highly lethal infections in compromised patients around the globe. C. neoformans typically initiates infections in mammalian lung tissue and subsequently disseminates to the central nervous system where it causes significant pathologies. Virulence genes of C. neoformans are being characterized at an increasing rate, however, we are far from a comprehensive understanding of their roles and genetic interactions. Some of these reported virulence genes are scattered throughout different databases, while others are not yet included...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27828843/increase-risk-of-allergic-diseases-in-patients-with-ankylosing-spondylitis-a-10-year-follow-up-population-based-study-in-taiwan
#13
Wei-Pin Chang, Chun-Nan Kuo, Li-Na Kuo, Yao-Tung Wang, Wuu-Tsun Perng, Ho-Chang Kuo, James Cheng-Chung Wei
Th2 and Th17 cells are both associated with developing ankylosing spondylitis (AS) and asthma. Th2 cells are also associated with allergic rhinitis and atopic dermatitis (AD). The prevalence of such allergic diseases in AS patients is unknown. In this study, we intended to study the risk of allergic diseases in a 10-year follow-up population of newly diagnosed patients with AS. We used a nationwide 10-year population-based database retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27826220/chitinase-3-like-1-is-produced-by-human-th17-cells-and-correlates-with-the-level-of-inflammation-in-juvenile-idiopathic-arthritis-patients
#14
Manuela Capone, Laura Maggi, Veronica Santarlasci, Maria Caterina Rossi, Alessio Mazzoni, Gianni Montaini, Rolando Cimaz, Matteo Ramazzotti, Marie Pierre Piccinni, Giusi Barra, Raffaele De Palma, Francesco Liotta, Enrico Maggi, Sergio Romagnani, Francesco Annunziato, Lorenzo Cosmi
BACKGROUND: CHI3L1 is a chitinase-like protein without enzymatic activity, produced by activated macrophages, chondrocytes, neutrophils. Recent studies on arthritis, asthma, and inflammatory bowel diseases suggest that chitinases are important in inflammatory processes and tissue remodeling, but their production by human T cells, has never been reported. METHODS: A microarray analysis of gene expression profile was performed on Th17 and classic Th1 cell clones and CHI3L1 was found among the up-regulated genes on Th17 cells...
2016: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/27817960/multifaceted-immune-responses-and-protective-efficacy-elicited-by-a-recombinant-autolyzed-salmonella-expressing-flic-flagellar-antigen-of-f18-escherichia-coli
#15
Gayeon Won, John Hwa Lee
Porcine edema disease (ED) caused by F18(+) Shiga toxin 2e-producing Escherichia coli (STEC) has imposed significant economic losses in the swine industry worldwide, resulting in sudden deaths in post-weaned piglets. The flagellin protein of F18(+) STEC, a structural component of the flagellar filament, is a known virulence factor that mediates adhesion and invasion to porcine epithelial cells. In this study, Salmonella inactivated by the E lysis gene and expressing the flagellin (fliC) antigen was genetically engineered utilizing a plasmid (pMMP184) carrying an efficient heterologous antigen delivery system...
December 7, 2016: Vaccine
https://www.readbyqxmd.com/read/27815572/phase-i-ii-study-of-lenalidomide-and-alemtuzumab-in-refractory-chronic-lymphocytic-leukemia-cll-effects-on-t-cells-and-immune-checkpoints
#16
Maria Winqvist, Fariba Mozaffari, Marzia Palma, Sandra Eketorp Sylvan, Lotta Hansson, Håkan Mellstedt, Anders Österborg, Jeanette Lundin
This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2...
November 4, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27798418/t2-low-asthma-current-approach-to-diagnosis-and-therapy
#17
Konstantinos Samitas, Eleftherios Zervas, Mina Gaga
PURPOSE OF REVIEW: Asthma is a heterogeneous disease not only on a clinical but also on a mechanistic level. For a long time, the molecular mechanisms of asthma were considered to be driven by type 2 helper T cells (Th2) and eosinophilic airway inflammation; however, extensive research has revealed that T2-low subtypes that differ from the dominant T2 paradigm are also common. RECENT FINDINGS: Research into asthma pathways has led to the recognition that some asthma phenotypes show absence of T2 inflammation or alternate between T2 and non-T2 responses...
January 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27793775/systemic-and-tumor-th1-and-th2-inflammatory-profile-and-macrophages-in-lung-cancer-influence-of-underlying-chronic-respiratory-disease
#18
Mercè Mateu-Jimenez, Víctor Curull, Lara Pijuan, Albert Sánchez-Font, Hugo Rivera-Ramos, Alberto Rodríguez-Fuster, Rafael Aguiló, Joaquim Gea, Esther Barreiro
INTRODUCTION: Chronic respiratory conditions, especially chronic obstructive pulmonary disease (COPD), and inflammatory events underlie lung cancer (LC). We hypothesized that profiles of T helper 1 and T helper 2 cytokines and type 1 and type 2 macrophages (M1 and M2) are differentially expressed in lung tumors and blood of patients with NSCLC with and without COPD and that the ratio M1/M2 specifically may influence their survival. METHODS: In blood, inflammatory cytokines (determined by enzyme-linked immunosorbent assay) were quantified in 80 patients with LC (60 with LC and COPD [the LC-COPD group] and 20 with LC only [the LC-only group]) and lung specimens (tumor and nontumor) from those undergoing thoracotomy (20 in the LC-COPD group and 20 in the LC-only group)...
October 25, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27783037/mir-155-a-novel-target-in-allergic-asthma
#19
REVIEW
Hong Zhou, Junyao Li, Peng Gao, Qi Wang, Jie Zhang
MicroRNAs (miRNAs), a class of small non-coding RNAs of 18-24 nucleotides in length, function to posttranscriptionally regulate protein expression. miR-155 was one of the first identified and, to date, the most studied miRNA, and has been linked to various cellular processes such as modulation of immune responses and oncogenesis. Previous studies have identified miR-155 as a crucial positive regulator of Th1 immune response in autoimmune diseases, but as a suppressor of Th2 immunity in allergic disorders. However, recent studies have found new evidence that miR-155 plays an indispensible role in allergic asthma...
October 24, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27782330/old-dogs-new-tricks-immunoregulatory-properties-of-c3-and-c5-cleavage-fragments
#20
REVIEW
Admar Verschoor, Christian M Karsten, Steven P Broadley, Yves Laumonnier, Jörg Köhl
The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes...
November 2016: Immunological Reviews
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