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https://www.readbyqxmd.com/read/28298605/cxcr5-dependent-entry-of-cd8-t-cells-into-rhesus-macaque-b-cell-follicles-achieved-through-t-cell-engineering
#1
Victor I Ayala, Claire Deleage, Matthew T Trivett, Sumiti Jain, Lori V Coren, Matthew W Breed, Joshua A Kramer, James A Thomas, Jacob D Estes, Jeffrey D Lifson, David E Ott
Follicular helper CD4 T cells, TFH, residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXCR5, the chemokine receptor implicated in cellular entry into B-cell follicles...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28288791/efficacy-and-safety-of-sofosbuvir-plus-daclatasvir-for-treatment-of-hcv-associated-cryoglobulinemia-vasculitis
#2
David Saadoun, Stanislas Pol, Yasmina Ferfar, Laurent Alric, Christophe Hezode, Si Nafa Si Ahmed, Luc de Saint Martin, Cloé Comarmond, Anne Sophie Bouyer, Lucile Musset, Thierry Poynard, Matthieu Resche Rigon, Patrice Cacoub
Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in about 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct acting antiviral drugs in these patients. We performed open-label, prospective, multi-center study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas...
March 10, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28282423/age-related-macular-degeneration-phenotypes-are-associated-with-increased-tumor-necrosis-alpha-and-subretinal-immune-cells-in-aged-cxcr5-knockout-mice
#3
Hu Huang, Ying Liu, Lei Wang, Wen Li
The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features...
2017: PloS One
https://www.readbyqxmd.com/read/28275192/oral-prion-disease-pathogenesis-is-impeded-in-the-specific-absence-of-cxcr5-expressing-dendritic-cells
#4
Barry M Bradford, Boris Reizis, Neil A Mabbott
After oral exposure the early replication of certain prion strains upon stromal-derived follicular dendritic cells (FDC) in the Peyer's patches in the small intestine is essential for the efficient spread of disease to the brain. However, little is known of how prions are initially conveyed from the gut lumen to establish infection on FDC. Our previous data suggest that mononuclear phagocytes such as CD11c(+) conventional dendritic cells play an important role in the initial propagation of prions from the gut lumen into Peyer's patches...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28274850/direct-acting-antiviral-therapy-restores-immune-tolerance-to-patients-with-hepatitis-c-virus-induced-cryoglobulinemia-vasculitis
#5
Cloé Comarmond, Marlène Garrido, Stanislas Pol, Anne-Claire Desbois, Myrto Costopoulos, Magali Le Garff-Tavernier, Si Nafa Si Ahmed, Laurent Alric, Hélène Fontaine, Bertrand Bellier, Anna Maciejewski, Michelle Rosenzwajg, David Klatzmann, Lucile Musset, Thierry Poynard, Patrice Cacoub, David Saadoun
BACKGROUND & AIMS: Interferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular immunity. METHODS: We performed a prospective study of 27 consecutive patients with HCV-CV (median age 59 years) treated with DAA therapy (21 patients received sofosbuvir plus ribavirin for 24 weeks, 4 patients received sofosbuvir plus daclatasvir for 12 weeks, and 2 patients received sofosbuvir plus simeprevir for 12 weeks) in Paris, France...
March 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28264017/ncoa1-is-a-novel-susceptibility-gene-for-multiple-myeloma-in-the-chinese-population-a-case-control-study
#6
Mengle Peng, Guanfei Zhao, Funing Yang, Guixue Cheng, Jing Huang, Xiaosong Qin, Yong Liu, Qingtao Wang, Yongzhe Li, Dongchun Qin
Multiple myeloma (MM) is an incurable malignancy of mature B-lymphoid cells, and its pathogenesis is only partially understood. Previous studies have demonstrated that a number of Non-Hodgkin Lymphoma (NHL) associated genes also show susceptibility to MM, suggesting malignancies originating from B cells may share similar genetic susceptibility. Several recent large-scale genome-wide association studies (GWAS) have identified HLA-I, HLA-II, CXCR5, ETS1, LPP and NCOA1 genes as genetic risk factors associated with NHL, and this study aimed to investigate whether these genes polymorphisms confer susceptibility with MM in the Chinese Han population...
2017: PloS One
https://www.readbyqxmd.com/read/28159893/dynamics-of-siv-specific-cxcr5-cd8-t-cells-during-chronic-siv-infection
#7
Geetha H Mylvaganam, Daniel Rios, Hadia M Abdelaal, Smita Iyer, Gregory Tharp, Maud Mavinger, Sakeenah Hicks, Ann Chahroudi, Rafi Ahmed, Steven E Bosinger, Ifor R Williams, Pamela J Skinner, Vijayakumar Velu, Rama R Amara
A significant challenge to HIV eradication is the elimination of viral reservoirs in germinal center (GC) T follicular helper (Tfh) cells. However, GCs are considered to be immune privileged for antiviral CD8 T cells. Here, we show a population of simian immunodeficiency virus (SIV)-specific CD8 T cells express CXCR5 (C-X-C chemokine receptor type 5, a chemokine receptor required for homing to GCs) and expand in lymph nodes (LNs) following pathogenic SIV infection in a cohort of vaccinated macaques. This expansion was greater in animals that exhibited superior control of SIV...
February 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28157399/cxcr5-cd8-t-cells-indirectly-offer-b-cell-help-and-are-inversely-correlated-with-viral-load-in-chronic-hepatitis-b-infection
#8
Hang Jiang, Linhai Li, Jiang Han, Zhiwei Sun, Yihui Rong, Yun Jin
Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5(+) CD8(+) T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5(+) CD8(+) T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5(+) CD8(+) T cells in peripheral blood, in which CXCR5(+) CD8(+) T cells were negatively correlated with the frequency of CXCR5(+) CD4(+) T cells in CHB patients...
February 3, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28155010/chemokine-cxcl13-activates-p38-mapk-in-the-trigeminal-ganglion-after-infraorbital-nerve-injury
#9
Qian Zhang, Ming-Di Zhu, De-Li Cao, Xue-Qiang Bai, Yong-Jing Gao, Xiao-Bo Wu
Recent data demonstrated that chemokine CXCL13 mediates neuroinflammation and contributes to the maintenance of neuropathic pain after nerve injury in the spinal cord. Pro-nociceptive chemokines activate mitogen-activated protein kinases (MAPKs) which are potential signaling pathways contributing to the nociceptive behavior in inflammatory or neuropathic pain. However, whether activation of p38 and JNK MAPK signaling pathway in the trigeminal ganglion (TG) are involved in CXCL13 and its receptor CXCR5-mediated orofacial pain has not yet been clarified...
February 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#10
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
February 1, 2017: Nature
https://www.readbyqxmd.com/read/28138558/circulating-cxcr5-cxcr3-pd-1-lo-tfh-like-cells-in-hiv-1-controllers-with-neutralizing-antibody-breadth
#11
Enrique Martin-Gayo, Jacqueline Cronin, Taylor Hickman, Zhengyu Ouyang, Madelene Lindqvist, Kellie E Kolb, Julian Schulze Zur Wiesch, Rafael Cubas, Filippos Porichis, Alex K Shalek, Jan van Lunzen, Elias K Haddad, Bruce D Walker, Daniel E Kaufmann, Mathias Lichterfeld, Xu G Yu
HIV-1-specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5(+)CXCR3(+)PD-1(lo) CD4(+) T cells...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28134081/detecting-novel-micro-rnas-in-rheumatoid-arthritis-with-gene-based-association-testing
#12
Aleksander Lenert, David W Fardo
OBJECTIVES: To identify novel risk genes by gene-based association analysis in rheumatoid arthritis (RA). METHODS: We performed gene-based association testing with GATES (Gene-based Association Test using Extended Simes procedure) to augment the power of genomewide-association study (GWAS) results from the largest meta-GWAS by Okada et al. in 14,361 RA cases and 43,923 controls of European ancestry using 8,694,488 SNPs. RESULTS: We identified 115 genes significantly associated with RA by gene-based association testing corresponding to 43 RA risk loci; 23 risk loci contained a single top risk gene, while 20 risk loci contained two or more risk genes...
January 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28130496/induction-of-il21-in-peripheral-t-follicular-helper-cells-is-an-indicator-of-influenza-vaccine-response-in-a-previously-vaccinated-hiv-infected-pediatric-cohort
#13
Lesley R de Armas, Nicola Cotugno, Suresh Pallikkuth, Li Pan, Stefano Rinaldi, M Celeste Sanchez, Louis Gonzalez, Alberto Cagigi, Paolo Rossi, Paolo Palma, Savita Pahwa
HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012-2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28126665/profiling-of-jejunum-inflammatory-gene-expression-during-murine-eimeriosis
#14
Mohamed A Dkhil, Mona Khalil, Saleh Al-Quraishy
To understand the host-parasite relationship during coccidiosis it is necessary to identify the transcriptional profile of the local host. In this study, gene profiling in the mouse jejunum due to infection with Eimeria papillata was investigated using Agilent microarray technology. On day 5 post-infection, the characterization of infected and non-infected mice jejunum transcriptional response was compared. There was an increase in the level of tumour necrosis factor-α, nitrite/nitrate and nitric oxide synthase activity was observed following infection...
March 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28122164/increased-circulating-cxcr5-cd4-t-follicular-helper-like-cells-in-oral-lichen-planus
#15
Ya-Qin Tan, Qing Li, Jing Zhang, Ge-Fei Du, Rui Lu, Gang Zhou
BACKGROUND: CD4(+) T helper cell is crucial for the inflammatory autoimmune condition of oral lichen planus (OLP). Recently, the pathogenetic functions of T follicular helper (Tfh) cells, a subtype of CD4(+) T helper cells, has been revealed in autoimmune diseases for their pivotal regulation on humoral immunity. To explore the potential pathophysiological role of Tfh cells in OLP, the expression of circulating Tfh-like cells and its correlations with IL-21 and B cells were investigated...
January 25, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28112376/increased-frequency-of-peripheral-blood-follicular-helper-t-cells-and-elevated-serum-il%C3%A2-21-levels-in-patients-with-knee-osteoarthritis
#16
Yuxing Shan, Changlin Qi, Yijun Liu, Hui Gao, Ding Zhao, Yanfang Jiang
An aberrant immune response has been implicated in the pathogenesis of osteoarthritis (OA). However, the role of peripheral blood follicular helper T (TFH) cells in the pathogenesis of OA has yet to be elucidated. The purpose of the present study was to examine the role of TFH cells and serum interleukin‑21 (IL‑21) in the pathogenesis of OA. Frequency of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD‑1)+, and IL‑21+ CXCR5+CD4+ T cells in 40 patients with OA and 13 healthy controls (HCs) were examined by flow cytometry...
January 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28108610/circulating-cxcr5-pd-1-icos-follicular-t-helper-cells-are-increased-close-to-the-diagnosis-of-type-1-diabetes-in-children-with-multiple-autoantibodies
#17
Tyyne Viisanen, Emmi-Leena Ihantola, Kirsti Näntö-Salonen, Heikki Hyöty, Noora Nurminen, Jenni Selvenius, Auni Juutilainen, Leena Moilanen, Jussi Pihlajamäki, Riitta Veijola, Jorma Toppari, Mikael Knip, Jorma Ilonen, Tuure Kinnunen
Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4(+)CXCR5(+) follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28017425/vaccination-of-rhesus-macaques-with-the-live-attenuated-hsv-1-vaccine-vc2-stimulates-the-proliferation-of-mucosal-t-cells-and-germinal-center-responses-resulting-in-sustained-production-of-highly-neutralizing-antibodies
#18
Brent A Stanfield, Bapi Pahar, Vladimir N Chouljenko, Ronald Veazey, Konstantin G Kousoulas
We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG1 after two booster vaccinations, while IgG subtypes IgG2 and IgG3 remained at low to undetectable levels...
January 23, 2017: Vaccine
https://www.readbyqxmd.com/read/28004828/analysis-of-cxcr5-th17-cells-in-relation-to-disease-activity-and-tnf-inhibitor-therapy-in-rheumatoid-arthritis
#19
Deepika Singh, Matthew Henkel, Bernadette Sendon, June Feng, Anthony Fabio, Diana Metes, Larry W Moreland, Mandy J McGeachy
Th17 and TfH cells are thought to promote tissue inflammation and autoantibody production, respectively, in autoimmune diseases including rheumatoid arthritis (RA). TfH cells that co-express Th17 markers (CXCR5(+)Th17) encompass both of these pathogenic functions, and are increased in some human autoimmune settings including juvenile dermatomyositis. We investigated CXCR5(+)Th17 cells in RA subjects with stable or active disease and before and after TNF inhibitor therapy. CXCR5(+)Th17 cell frequency was increased in RA compared to healthy controls, but other helper T cell subsets were not different...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28002487/long-term-transcriptomic-effects-of-prebiotics-and-synbiotics-delivered-in-ovo-in-broiler-chickens
#20
Anna Slawinska, Arkadiusz Plowiec, Maria Siwek, Marcin Jaroszewski, Marek Bednarczyk
In ovo delivery of prebiotics and synbiotics in chickens allows for the development of intestinal microflora prior to hatching, which boosts their robustness. The goal of this study was to determine the transcriptomic profile of the spleen (S), cecal tonsils (CT), and large intestine (LI) of adult chickens injected with prebiotics and synbiotics in ovo. On day 12 of embryo development, incubating eggs were injected with prebiotics: inulin alone (P1) or in combination with Lactococcus lactis subsp. lactis IBB2955 (S1), galactooligosaccharides (GOS) alone (P2) or in combination with Lactococcus lactis subsp...
2016: PloS One
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