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https://www.readbyqxmd.com/read/30515983/filaggrin-null-mutations-are-associated-with-altered-circulating-tregs-in-atopic-dermatitis
#1
Verena Moosbrugger-Martinz, Robert Gruber, Katharina Ladstätter, Marion Bellutti, Stefan Blunder, Matthias Schmuth, Sandrine Dubrac
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathogenesis. Although regulatory T cells (Tregs) have previously been studied in AD, their role remains controversial, likely owing to patient heterogeneity. Thus, we recruited adult AD patients and age-matched healthy controls, and assessed their filaggrin (FLG) genotype, serum IgE level, and eczema area and severity index (EASI). We found increased proportions of all circulating Treg subpopulations in AD patients. Moreover, we show positive correlations between circulating Tregs and serum IgE FLG null mutations limited the expansion of both memory and effector Tregs and enhanced that of recently thymus-emigrated Tregs...
December 4, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/30510966/phenotypic-characterization-of-circulating-cd4-t-cells-in-anca-associated-vasculitis
#2
Sandra Lilliebladh, Åsa Johansson, Åsa Pettersson, Sophie Ohlsson, Thomas Hellmark
T cell-mediated immune responses are thought to play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody- (ANCA-) associated vasculitides (AAV). CD4+ T cells can be divided into subsets depending on their expression of chemokine receptors. In this study, different CD4+ T cell populations in patients with AAV were analysed and compared to healthy blood donors as well as therapy controls. 18 patients with active AAV, 46 in remission, 21 healthy controls (HBD), and 15 therapy controls (TC) were enrolled...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/30510928/host-cell-rab-gtpases-in-hepatitis-b-virus-infection
#3
REVIEW
Lisa Zeyen, Reinhild Prange
Hepatitis B virus (HBV) is a leading cause of liver disease and is presently estimated to infect more than 250 million humans. The extremely successful spread of this virus among the human population is explained by its effective transmission strategies and its manifold particle types, including virions, empty envelopes and naked capsids. Due to its tiny genome, HBV depends on cellular machineries to thrive in infected hepatocytes. To enter, traverse and exit the cell, HBV exploits host membrane trafficking pathways, including intracellular highways directed by Rab GTPases...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/30508721/roughness-of-transmembrane-helices-reduces-lipid-membrane-dynamics
#4
Marie Olšinová, Piotr Jurkiewicz, Iryna Kishko, Jan Sýkora, Ján Sabó, Martin Hof, Lukasz Cwiklik, Marek Cebecauer
The dynamics of cellular membranes is primarily determined by lipid species forming a bilayer. Proteins are considered mainly as effector molecules of diverse cellular processes. In addition to large assemblies of proteins, which were found to influence properties of fluid membranes, biological membranes are densely populated by small, highly mobile proteins. However, little is known about the effect of such proteins on the dynamics of membranes. Using synthetic peptides, we demonstrate that transmembrane helices interfere with the mobility of membrane components by trapping lipid acyl chains on their rough surfaces...
November 20, 2018: iScience
https://www.readbyqxmd.com/read/30505301/update-on-pd-1-pd-l1-inhibitors-in-multiple-myeloma
#5
REVIEW
Tomas Jelinek, Bruno Paiva, Roman Hajek
The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Their current application in multiple myeloma (MM) is rather uncertain, as discordant results have been reported by distinct research groups concerning especially the expression of PD-1/PD-L1 molecules on malignant plasma cells or on the responsible immune effector cell populations, respectively...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30503835/the-jak-stat1-transcriptional-signature-in-peripheral-immune-cells-reveals-alterations-related-to-illness-duration-and-acuity-in-psychosis
#6
Jennifer K Melbourne, Cherise Rosen, Benjamin Feiner, Yanzhen Pang, Rajiv P Sharma
Multiple lines of inquiry demonstrate alterations to immune function in psychosis. Clinically, this is reflected by elevated proinflammatory cytokines in serum, indicating activation of circulating immune cells. Data from isolated cells in clinical populations support the presence of altered activity of pertinent intracellular signaling pathways. Here, we focus on the well-characterized IFN-γ mediated JAK-STAT1 signaling pathway, which is involved in multiple aspects of immunity, including activation of circulating immune cells to a proinflammatory phenotype...
November 29, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/30500874/a-genome-wide-association-study-identifying-rap1a-as-a-novel-susceptibility-gene-for-crohn-s-disease-in-japanese-individuals
#7
Yoichi Kakuta, Yosuke Kawai, Takeo Naito, Atsushi Hirano, Junji Umeno, Yuta Fuyuno, Zhenqiu Liu, Dalin Li, Takeru Nakano, Yasuhiro Izumiyama, Ryo Ichikawa, Daisuke Okamoto, Hiroshi Nagai, Shin Matsumoto, Katsutoshi Yamamoto, Naonobu Yokoyama, Hirofumi Chiba, Yusuke Shimoyama, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Jun Yasuda, Motohiro Esaki, Katsushi Tokunaga, Minoru Nakamura, Takayuki Matsumoto, Dermot P B McGovern, Masao Nagasaki, Yoshitaka Kinouchi, Tooru Shimosegawa, Atsushi Masamune
Background and Aims: Genome-wide association studies (GWASs) of European populations have identified numerous susceptibility loci for Crohn's disease (CD). Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array (JPA) and subsequent imputation with the 1KJPN reference panel. Methods: Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included...
November 29, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/30500825/de-novo-mutations-in-the-gtp-gdp-binding-region-of-rala-a-ras-like-small-gtpase-cause-intellectual-disability-and-developmental-delay
#8
Susan M Hiatt, Matthew B Neu, Ryne C Ramaker, Andrew A Hardigan, Jeremy W Prokop, Miroslava Hancarova, Darina Prchalova, Marketa Havlovicova, Jan Prchal, Viktor Stranecky, Dwight K C Yim, Zöe Powis, Boris Keren, Caroline Nava, Cyril Mignot, Marlene Rio, Anya Revah-Politi, Parisa Hemati, Nicholas Stong, Alejandro D Iglesias, Sharon F Suchy, Rebecca Willaert, Ingrid M Wentzensen, Patricia G Wheeler, Lauren Brick, Mariya Kozenko, Anna C E Hurst, James W Wheless, Yves Lacassie, Richard M Myers, Gregory S Barsh, Zdenek Sedlacek, Gregory M Cooper
Mutations that alter signaling of RAS/MAPK-family proteins give rise to a group of Mendelian diseases known as RASopathies. However, among RASopathies, the matrix of genotype-phenotype relationships is still incomplete, in part because there are many RAS-related proteins and in part because the phenotypic consequences may be variable and/or pleiotropic. Here, we describe a cohort of ten cases, drawn from six clinical sites and over 16,000 sequenced probands, with de novo protein-altering variation in RALA, a RAS-like small GTPase...
November 30, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/30500711/immune-responses-induced-by-different-genotypes-of-the-disease-specific-protein-of-rice-stripe-virus-in-the-vector-insect
#9
Wan Zhao, Qianshuo Wang, Zhongtian Xu, Renyi Liu, Feng Cui
Persistent plant viruses circulate between host plants and vector insects, possibly leading to the genetic divergence in viral populations. We analyzed the single nucleotide polymorphisms (SNPs) of Rice stripe virus (RSV) when it incubated in the small brown planthopper and rice. Two SNPs, which lead to nonsynonymous substitutions in the disease-specific protein (SP) of RSV, produced three genotypes, i.e., GG, AA and GA. The GG type mainly existed in the early infection period of RSV in the planthoppers and was gradually substituted by the other two genotypes during viral transmission...
November 27, 2018: Virology
https://www.readbyqxmd.com/read/30498201/tipping-the-balance-inhibitory-checkpoints-in-intestinal-homeostasis
#10
REVIEW
Maria E Joosse, Iris Nederlof, Lucy S K Walker, Janneke N Samsom
The small intestinal and colonic lamina propria are populated with forkhead box P3 (FOXP3)+ CD4+ regulatory T cells (Tregs) and interleukin-10-producing T cells that orchestrate intestinal tolerance to harmless microbial and food antigens. Expression of co-inhibitory receptors such as CTLA-4 and PD-1 serve as checkpoints to these cells controlling their T-cell receptor (TCR)-mediated and CD28-mediated activation and modulating the phenotype of neighboring antigen presenting cells. Recent discoveries on the diversity of co-inhibitory receptors and their selective cellular expression has shed new light on their tissue-dependent function...
November 29, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/30498094/expression-of-pd-1-by-t-cells-in-malignant-glioma-patients-reflects-exhaustion-and-activation
#11
Tom B Davidson, Alexander H Lee, Melody Hsu, Shaina Sedighim, Joey Orpilla, Janet Treger, Maximilian Mastall, Saskia Roesch, Carmen Rapp, Mildred Galvez, Aaron Y Mochizuki, Joseph P Antonios, Alejandro J Garcia, Nikesh Kotecha, Nicholas L Bayless, David A Nathanson, Anthony C Wang, Richard G Everson, William H Yong, Timothy F Cloughesy, Linda M Liau, Christel C Herold-Mende, Robert M Prins
PURPOSE: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent pre-clinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective anti-tumor T cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in malignant glioma patients. EXPERIMENTAL DESIGN: In this study, we examined the immune landscape and function of PD-1 expression on T cells from the tumor and peripheral blood in malignant glioma patients...
November 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30498016/integral-gene-drives-for-population-replacement
#12
Alexander Nash, Giulia Mignini Urdaneta, Andrea K Beaghton, Astrid Hoermann, Philippos Aris Papathanos, George K Christophides, Nikolai Windbichler
A first generation of CRISPR-based gene drives have now been tested in the laboratory in a number of organisms including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of Integral Gene Drive (IGD) as an alternative paradigm for population replacement...
November 29, 2018: Biology Open
https://www.readbyqxmd.com/read/30496498/chemokine-regulated-recruitment-of-antigen-specific-t-cell-sub-populations-to-the-liver-in-acute-and-chronic-hepatitis-c-infection
#13
Mehdi R Pirozyan, Nam Nguyen, Barbara Cameron, Fabio Luciani, Rowena A Bull, Amany Zekry, Andrew R Lloyd
Background: In hepatitis C virus (HCV) infection, virus-specific CD8+ T cells are recruited to the liver for antiviral activity. Multiple chemokine ligands are induced by the infection, notably interferon-inducible chemokine, CXCL10. In HCV, intra-hepatic T cells express chemokine receptors (CCRs), including CXCR3, CXCR6, CCR1, and CCR5, but CCR expression on antigen-specific effector and memory T cells has not been investigated. Methods: Paired blood and liver samples were collected from subjects with chronic HCV for flow cytometric analysis of CCR expression on CD8+ T cells...
November 29, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/30487281/unique-type-i-interferon-expansion-survival-cytokines-and-jak-stat-gene-signatures-of-multi-functional-hsv-specific-effector-memory-cd8-t-em-cells-are-associated-with-asymptomatic-ocular-herpes-in-humans
#14
Hawa Vahed, Anshu Agrawal, Ruchi Srivastava, Swayam Prakash, Pierre-Gregoire A Coulon, Soumyabrata Roy, Lbachir BenMohamed
A large proportion of the world population harbors herpes simplex virus type 1 (HSV-1) a major cause of infectious corneal blindness. HSV-specific CD8+ T cells protect from herpes infection and disease. However, the genomic, phenotypic and functional characteristics of CD8+ T cells associated with the protection seen in asymptomatic (ASYMP) individuals, who despite being infected, never experienced any recurrent herpetic disease, remains to be fully elucidated. In this investigation, we compared the phenotype, function, and level of expression of a comprehensive panel of 579 immune genes of memory CD8+ T cells, sharing the same HSV-1 epitope-specificities, and freshly isolated peripheral blood from well-characterized cohorts of protected ASYMP and non-protected symptomatic (SYMP) individuals, with a history of numerous episodes of recurrent herpetic disease using high throughput digital NanoString nCounter™ system and Flow Cytometry...
November 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30483514/conformational-change-induced-by-putidaredoxin-binding-to-ferrous-co-ligated-cytochrome-p450cam-characterized-by-2d-ir-spectroscopy
#15
Sashary Ramos, Edward J Basom, Megan C Thielges
The importance of conformational dynamics to protein function is now well-appreciated. An outstanding question is whether they are involved in the effector role played by putidaredoxin (Pdx) in its reduction of the O2 complex of cytochrome P450cam (P450cam), an archetypical member of the cytochrome P450 superfamily. Recent studies have reported that binding of Pdx induces a conformational change from a closed to an open state of ferric P450cam, but a similar conformational change does not appear to occur for the ferrous, CO-ligated enzyme...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/30483269/hvem-and-cd160-regulators-of-immunopathology-during-malaria-blood-stage
#16
Franziska Muscate, Nadine Stetter, Christoph Schramm, Julian Schulze Zur Wiesch, Lidia Bosurgi, Thomas Jacobs
CD8+ T cells are key players during infection with the malaria parasite Plasmodium berghei ANKA (PbA). While they cannot provide protection against blood-stage parasites, they can cause immunopathology, thus leading to the severe manifestation of cerebral malaria. Hence, the tight control of CD8+ T cell function is key in order to prevent fatal outcomes. One major mechanism to control CD8+ T cell activation, proliferation and effector function is the integration of co-inhibitory and co-stimulatory signals. In this study, we show that one such pathway, the HVEM-CD160 axis, significantly impacts CD8+ T cell regulation and thereby the incidence of cerebral malaria...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30483230/a-strain-of-an-emerging-indian-xanthomonas-oryzae-pv-oryzae-pathotype-defeats-the-rice-bacterial-blight-resistance-gene-xa13-without-inducing-a-clade-iii-sweet-gene-and-is-nearly-identical-to-a-recent-thai-isolate
#17
Sara C D Carpenter, Prashant Mishra, Chandrika Ghoshal, Prasanta K Dash, Li Wang, Samriti Midha, Gouri S Laha, Jagjeet S Lore, Wichai Kositratana, Nagendra K Singh, Kuldeep Singh, Prabhu B Patil, Ricardo Oliva, Sujin Patarapuwadol, Adam J Bogdanove, Rhitu Rai
The rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae ( Xoo ) injects transcription activator-like effectors (TALEs) that bind and activate host "susceptibility" ( S ) genes important for disease. Clade III SWEET genes are major S genes for bacterial blight. The resistance genes xa5 , which reduces TALE activity generally, and xa13 , a SWEET11 allele not recognized by the cognate TALE, have been effectively deployed. However, strains that defeat both resistance genes individually were recently reported in India and Thailand...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30479379/models-of-immune-selection-for-multi-locus-antigenic-diversity-of-pathogens
#18
REVIEW
Maria Georgieva, Caroline O Buckee, Marc Lipsitch
It is well accepted that pathogens can evade recognition and elimination by the host immune system by varying their antigenic targets. Thus, it has become a truism that host immunity is a major driver and determinant of the antigenic diversity of pathogens. However, it remains puzzling how host immunity selects for antigenic diversity at the level of the pathogen population, given that hosts have acquired immune responses to multiple antigens of most pathogens - sometimes through multiple effectors of both humoral and cellular immunity...
November 27, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/30474472/long-noncoding-rna-malat1-is-not-essential-for-t-cell-development-and-response-to-lcmv-infection
#19
Yingpeng Yao, Wenhui Guo, Jingjing Chen, Pingting Guo, Guotao Yu, Juanjuan Liu, Fang Wang, Jingjing Liu, Menghao You, Tianyan Zhao, Youmin Kang, Xi Ma, Shuyang Yu
Long noncoding RNAs (lncRNAs) are emerging as critical mediators of various biological processes in the immune system. The current data showed that the lncRNA Malat1 is highly expressed in T cell subsets, but the function of Malat1 in T cell remains unclear. In this study, we detected the T cell development and both CD8+ and CD4+ T cell response to LCMV infection using Malat1-/- mice model. To our surprise, there were no significant defects in thymocytes at different developmental stages and the peripheral T cell pool with ablation of Malat1...
November 26, 2018: RNA Biology
https://www.readbyqxmd.com/read/30469323/dops-adjuvant-confers-enhanced-protection-against-malaria-for-vlp-trap-based-vaccines
#20
Gustavo Cabral-Miranda, Ahmed M Salman, Mona O Mohsen, Federico L Storni, Elisa S Roesti, Murray A Skinner, Matthew D Heath, Matthias F Kramer, Shahid M Khan, Chris J Janse, Adrian V S Hill, Martin F Bachmann
Vaccination remains the most effective and essential prophylactic tool against infectious diseases. Enormous efforts have been made to develop effective vaccines against malaria but successes remain so far limited. Novel adjuvants may offer a significant advantage in the development of malaria vaccines, in particular if combined with inherently immunogenic platforms, such as virus-like particles (VLP). Dioleoyl phosphatidylserine (DOPS), which is expressed on the outer surface of apoptotic cells, represents a novel adjuvant candidate that may confer significant advantage over existing adjuvants, such as alum...
November 21, 2018: Diseases (Basel)
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