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https://www.readbyqxmd.com/read/29674500/novel-gpr34-and-ccr6-mutation-and-distinct-genetic-profiles-in-malt-lymphomas-of-different-sites
#1
Sarah Moody, Joe Sneath Thompson, Shih-Sung Chuang, Hongxiang Liu, Markus Raderer, George Vassiliou, Iwona Wlodarska, Fangtian Wu, Sergio Cogliatti, Alistair Robson, Margaret Ashton-Key, Yingwen Bi, John Goodlad, Ming-Qing Du
MALT lymphoma originates from a background of diverse chronic inflammatory disorders at various anatomic sites. The genetics underlying its development, particularly in those associated with autoimmune disorders, is poorly characterised. By whole exome sequencing of 21 cases of MALT lymphomas of the salivary gland and thyroid, we have identified recurrent somatic mutations in 2 G-protein coupled receptors (GPR34 and CCR6) not previously reported in human malignancies, 3 genes (PIK3CD, TET2, TNFRSF14) not previously implicated in MALT lymphoma, and a further 2 genes (TBL1XR1, NOTCH1) recently described in MALT lymphoma...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29670615/distinct-in-vitro-t-helper-17-differentiation-capacity-of-peripheral-naive-t-cells-in-rheumatoid-and-psoriatic-arthritis
#2
Eszter Baricza, Nikolett Marton, Panna Királyhidi, Orsolya Tünde Kovács, Ilona Kovácsné Székely, Eszter Lajkó, Lászó Kőhidai, Bernadett Rojkovich, Barbara Érsek, Edit Irén Buzás, György Nagy
Background: The T-helper 17 (Th17) cells have a prominent role in inflammation as well as in bone and join destruction in both rheumatoid and psoriatic arthritis (RA and PsA). Here, we studied Th17 cell differentiation in RA and PsA. Methods: Blood samples from healthy donors, RA and PsA patients were collected. CD45RO- (naive) and CD45RO+ (memory) T cells were isolated from peripherial blood mononuclear cell by magnetic separation. Naive T cells were stimulated with anti-CD3, anti-CD28, and goat anti-mouse IgG antibodies and treated with transforming grow factor beta, interleukin (IL)-6, IL-1β , and IL-23 cytokines and also with anti-IL-4 antibody...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669853/cd32-is-expressed-on-cells-with-transcriptionally-active-hiv-but-does-not-enrich-for-hiv-dna-in-resting-t-cells
#3
Mohamed Abdel-Mohsen, Leticia Kuri-Cervantes, Judith Grau-Exposito, Adam M Spivak, Racheal A Nell, Costin Tomescu, Surya Kumari Vadrevu, Leila B Giron, Carla Serra-Peinado, Meritxell Genescà, Josep Castellví, Guoxin Wu, Perla M Del Rio Estrada, Mauricio González-Navarro, Kenneth Lynn, Colin T King, Sai Vemula, Kara Cox, Yanmin Wan, Qingsheng Li, Karam Mounzer, Jay Kostman, Ian Frank, Mirko Paiardini, Daria Hazuda, Gustavo Reyes-Terán, Douglas Richman, Bonnie Howell, Pablo Tebas, Javier Martinez-Picado, Vicente Planelles, Maria J Buzon, Michael R Betts, Luis J Montaner
The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH 2 phenotype as defined by CXCR3, CCR4, and CCR6...
April 18, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29659729/t-helper-17-1-cells-associate-with-multiple-sclerosis-disease-activity-perspectives-for-early-intervention
#4
Jamie van Langelaar, Roos M van der Vuurst de Vries, Malou Janssen, Annet F Wierenga-Wolf, Isis M Spilt, Theodora A Siepman, Wendy Dankers, Georges M G M Verjans, Helga E de Vries, Erik Lubberts, Rogier Q Hintzen, Marvin M van Luijn
Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients...
April 5, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29618121/precision-medicine-using-different-biological-dmards-based-on-characteristic-phenotypes-of-peripheral-t-helper-cells-in-psoriatic-arthritis
#5
Ippei Miyagawa, Shingo Nakayamada, Kazuhisa Nakano, Satoshi Kubo, Shigeru Iwata, Yusuke Miyazaki, Maiko Yoshikawa, Hiroko Yoshinari, Yoshiya Tanaka
Objectives: We sought to investigate the selection of specific biological DMARDs (bDMARDs) based on characteristic lymphocyte phenotypes for treating PsA. Methods: Of 64 patients with PsA resistant to MTX, 26 underwent bDMARDs therapy selected according to phenotypic differences in peripheral helper T cells on 8-colour flow cytometry. The efficacies of this strategic treatment and the standard treatment administered to the other 38 patients were evaluated at 6 months...
April 2, 2018: Rheumatology
https://www.readbyqxmd.com/read/29602771/transcriptomic-analysis-of-cd4-t-cells-reveals-novel-immune-signatures-of-latent-tuberculosis
#6
Julie G Burel, Cecilia S Lindestam Arlehamn, Nabeela Khan, Grégory Seumois, Jason A Greenbaum, Randy Taplitz, Robert H Gilman, Mayuko Saito, Pandurangan Vijayanand, Alessandro Sette, Bjoern Peters
In the context of infectious diseases, cell population transcriptomics are useful to gain mechanistic insight into protective immune responses, which is not possible using traditional whole-blood approaches. In this study, we applied a cell population transcriptomics strategy to sorted memory CD4 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and gain insight into the phenotype of tuberculosis (TB)-specific CD4 T cells. We found a 74-gene signature that could discriminate between memory CD4 T cells from healthy latently Mycobacterium tuberculosis -infected subjects and noninfected controls...
March 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29582477/immune-molecular-profiling-of-whole-blood-drawn-from-a-non-human-primate-cardiac-xenograft-model-treated-with-anti-cd154-monoclonal-antibodies
#7
Sun A Ock, Keon Bong Oh, Seongsoo Hwang, Ik Jin Yun, Curie Ahn, Hyun Ken Chee, Hwajung Kim, Imran Ullah, Gi-Sun Im, Eung Woo Park
Most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. Here, we performed immune molecular profiling following anti-CD154 monoclonal antibody (mAb) treatment in heterotopic abdominal cardiac xenografts from α-1,3-galactosyltransferase-knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. Blood samples were collected from healthy monkeys as control and then at 2 days after xenograft transplantation and just before humane euthanasia; 94 genes related to the immune system were analyzed...
March 26, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29560431/cd4-t-cells-react-to-local-increase-of-%C3%AE-synuclein-in-a-pathology-associated-variant-dependent-manner-and-modify-brain-microglia-in-absence-of-brain-pathology
#8
Mads N Olesen, Josefine R Christiansen, Steen Vang Petersen, Poul Henning Jensen, Wojciech Paslawski, Marina Romero-Ramos, Vanesa Sanchez-Guajardo
We have previously shown that immunological processes in the brain during α-synuclein-induced neurodegeneration vary depending on the presence or absence of cell death. This suggests that the immune system is able to react differently to the different stages of α-synuclein pathology. However, it was unclear whether these immune changes were governed by brain processes or by a direct immune response to α-synuclein modifications. We have herein locally increased the peripheral concentration of α-synuclein or its pathology-associated variants, nitrated or fibrillar, to characterize the modulation of the CD4 T cell pool by α-synuclein and brain microglia in the absence of any α-synuclein brain pathology...
January 2018: Heliyon
https://www.readbyqxmd.com/read/29559470/autocrine-adenosine-regulates-tumor-polyfunctional-cd73-cd4-effector-t-cells-devoid-of-immune-checkpoints
#9
Nicolas Gourdin, Marion Bossennec, Céline Rodriguez, Selena Vigano, Christelle Machon, Camilla Jandus, David Bauché, Julien Faget, Isabelle Durand, Nicolas Chopin, Olivier Tredan, Julien C Marie, Bertrand Dubois, Jérôme Guitton, Pedro Romero, Christophe Caux, Christine Ménétrier-Caux
The production of CD73-derived Adenosine (Ado) by Tregs, has been proposed as a resistance mechanism to anti-PD1 therapy in murine tumor models. We reported that Human Tregs express the ecto-nucleotidase CD39, that generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4+ T cells (Teffs), enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6 and MDR1 and production of IL-17A/IFN-γ/IL-22/GM-CSF. CD39+ Tregs selectively targeted CD73+ Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73+ Teffs to secrete IL-17A...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29552015/the-phosphorylation-of-ccr6-on-distinct-ser-thr-residues-in-the-carboxyl-terminus-differentially-regulates-biological-function
#10
Mei-Yi Lu, Syuan-Shao Lu, Shiann-Luen Chang, Fang Liao
CCR6 is a G protein-coupled receptor (GPCR) that recognizes a single chemokine ligand, CCL20 and is primarily expressed by leukocytes. Upon ligand binding, CCR6 activates Gαi heterotrimeric G proteins to induce various potential cellular outcomes through context-specific cell signaling. It is well known that differential phosphorylation of Ser and Thr residues in the C-terminal domains or intracellular loops of GPCRs can generate barcodes that regulate GPCR function by regulating the recruitment of β-arrestins...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29551031/-brain-derived-neurotrophic-factor-enhances-the-role-of-mesenchymal-stem-cells-in-inhibiting-follicular-helper-t-cells
#11
S N Yang, X Pu, S L Xiang, J P Chen, L Pei
Objective: To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T cells (Tfh cells). Methods: The contents of indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-β and IL-21 in MSC culture supernatant were detected by ELISA; The peripheral blood of healthy volunteers were collected, and lymphocyte in peripheral blood was separated by human lymphocyte separation solution; Co-cultures of MSC and lymphocyte were performed by Transwell chamber, and the proportion of CD4(+)CXCR5(+) Tfh cells and their subtypes were detected by flow cytometry...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29545791/functional-antigen-specific-stem-cell-memory-t-scm-cd4-t-cells-are-induced-by-human-mycobacterium-tuberculosis-infection
#12
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29535421/astrocyte-derived-ccl20-reinforces-hif-1-mediated-hypoxic-responses-in-glioblastoma-by-stimulating-the-ccr6-nf-%C3%AE%C2%BAb-signaling-pathway
#13
Peng Jin, Seung-Hyun Shin, Yang-Sook Chun, Hyun-Woo Shin, Yong Jae Shin, Yeri Lee, Donggeon Kim, Do-Hyun Nam, Jong-Wan Park
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells...
March 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29526632/contribution-of-sex-steroids-and-prolactin-to-the-modulation-of-t-and-b-cells-during-autoimmunity
#14
REVIEW
Gabriela Recalde, Tamara Moreno-Sosa, Florencia Yúdica, Cristian A Quintero, María Belén Sánchez, Graciela A Jahn, Alexis M Kalergis, Juan Pablo Mackern-Oberti
In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of non- reproductive tissues. In the immune system, several studies with experimental models for SLE have shown a noticeable pro-inflammatory role for ERα, contributing to disease development reflected in proteinuria and renal pathology. On the other hand, ERβ appears to have an anti- inflammatory and immunosuppressive effect...
May 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29518422/egg-specific-ige-and-basophil-activation-but-not-egg-specific-t-cells-correlate-with-phenotypes-of-clinical-egg-allergy
#15
M Cecilia Berin, Alexander Grishin, Madhan Masilamani, Donald Y Leung, Scott H Sicherer, Stacie M Jones, A Wesley Burks, Alice K Henning, Peter Dawson, Joanna Grabowska, Charuta Agashe, Wendy F Davidson, Robert A Wood, Hugh A Sampson
BACKGROUND: Egg allergy is phenotypically heterogeneous. A subset of egg allergic individuals can tolerate egg in an extensively heated form. Inclusion of baked-egg (BE) into their diet accelerates resolution of egg allergy. Conversely, BE reactivity is associated with persistent disease. The immune basis of this clinical heterogeneity is unknown. OBJECTIVES: To study egg-specific antibody, basophil, and T cell responses in children with reactivity or tolerance to BE...
March 5, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29515587/t-cell-phenotype-and-t-cell-receptor-repertoire-in-patients-with-major-depressive-disorder
#16
Kostas Patas, Anne Willing, Cüneyt Demiralay, Jan Broder Engler, Andreea Lupu, Caren Ramien, Tobias Schäfer, Christian Gach, Laura Stumm, Kenneth Chan, Marissa Vignali, Petra C Arck, Manuel A Friese, Ole Pless, Klaus Wiedemann, Agorastos Agorastos, Stefan M Gold
While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross-sectional case-control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities ( n  = 20), who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject ( n  = 20)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29507584/clinical-implications-of-cd4-t-cell-subsets-in-adult-atopic-asthma-patients
#17
Matthew Wiest, Katherine Upchurch, Wenjie Yin, Jerome Ellis, Yaming Xue, Bobby Lanier, Mark Millard, HyeMee Joo, SangKon Oh
Background: T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood. Methods: We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity...
2018: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/29484182/regulatory-t-cells-in-renal-disease
#18
REVIEW
Maliha A Alikhan, Megan Huynh, A Richard Kitching, Joshua D Ooi
The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen-specific Tregs in HLA-mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29469805/c-ebp%C3%AE-drives-interactions-between-human-mait-cells-and-endothelial-cells-that-are-important-for-extravasation
#19
Chang Hoon Lee, Hongwei H Zhang, Satya P Singh, Lily Koo, Juraj Kabat, Hsinyi Tsang, Tej Pratap Singh, Joshua M Farber
Many mediators and regulators of extravasation by bona fide human memory-phenotype T cells remain undefined. Mucosal-associated invariant T (MAIT) cells are innate-like, anti-bacterial cells that we found excelled at crossing inflamed endothelium. They displayed abundant selectin ligands, with high expression of FUT7 and ST3GAL4 , and expressed CCR6, CCR5, and CCR2, which played non-redundant roles in trafficking on activated endothelial cells. MAIT cells selectively expressed CCAAT/enhancer-binding protein delta (C/EBPδ)...
February 22, 2018: ELife
https://www.readbyqxmd.com/read/29459864/blood-cxcr3-cd4-t-cells-are-enriched-in-inducible-replication-competent-hiv-in-aviremic-antiretroviral-therapy-treated-individuals
#20
Riddhima Banga, Francesco A Procopio, Alessandra Ruggiero, Alessandra Noto, Khalid Ohmiti, Matthias Cavassini, Jean-Marc Corpataux, William A Paxton, Georgios Pollakis, Matthieu Perreau
We recently demonstrated that lymph nodes (LNs) PD-1+ /T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals...
2018: Frontiers in Immunology
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