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https://www.readbyqxmd.com/read/28453759/randomised-double-blind-placebo-controlled-trial-of-ccr9-targeted-leukapheresis-treatment-of-ulcerative-colitis-patients
#1
Michael Eberhardson, Per Karlén, Ludvig Linton, Petra Jones, Annelie Lindberg, Martina Jones Kostalla, Emma Lindh, Anders Odén, Hans Glise, Ola Winqvist
Background and Aims: Ulcerative colitis patients display increased numbers of circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DRhi] monocytes expressing high levels of the gut-homing C-C chemokine receptor 9 [CCR9] and tumour necrosis factor [TNF]-α. The aim of this first-in-human, double-blind, randomised, placebo-controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis, with regards to safety, tolerability, and immunological response...
May 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28428786/challenge-of-humans-with-wild-type-salmonella-enterica-serovar-typhi-elicits-changes-in-the-activation-and-homing-characteristics-of-mucosal-associated-invariant-t-cells
#2
Rosângela Salerno-Goncalves, David Luo, Stephanie Fresnay, Laurence Magder, Thomas C Darton, Claire Jones, Claire S Waddington, Christoph J Blohmke, Brian Angus, Myron M Levine, Andrew J Pollard, Marcelo B Sztein
Gastrointestinal infections by Salmonella enterica serovar Typhi (S. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.9 million new cases annually and significant mortality when untreated. Recently, we provided the first direct evidence that CD8(+) MAIT cells are activated and have the potential to kill cells exposed to S. Typhi, and that these responses are dependent on bacterial load. However, MAIT cell kinetics and function during bacterial infections in humans remain largely unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28387445/stimulation-of-oral-fibroblast-chemokine-receptors-identifies-ccr3-and-ccr4-as-potential-wound-healing-targets
#3
Jeroen Kees Buskermolen, Sanne Roffel, Susan Gibbs
The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1 and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1 and XCL1) were used to study the activation of these receptors on gingiva fibroblasts...
April 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28380463/wnt5a-and-ccl25-promote-adult-t-cell-acute-lymphoblastic-leukemia-cell-migration-invasion-and-metastasis
#4
Xinzhou Deng, Zhenbo Tu, Meng Xiong, Kingsley Tembo, Lu Zhou, Pan Liu, Shan Pan, Jie Xiong, Xiangyong Yang, Jun Leng, Qian Zhang, Ruijing Xiao, Qiuping Zhang
Adult T-cell acute lymphoblastic leukemia (T-ALL) is a refractory leukemia. We previously showed that CCL25/CCR9 promotes T-ALL metastasis. In the present study, we assessed the effects of CCL25 on Wnt expression and the effects of Wnt5a and CCL25 on PI3K/Akt and RhoA activation. Transwell assays and mouse xenograft experiments were utilized to assess the effects of Wnt5a and CCL25 on MOLT4 cell invasion, migration and metastasis. The effects of Wnt5a on MOLT4 cell actin polarization and pseudopodium formation were examined using laser scanning confocal microscopy and scanning electron microscopy...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28370539/rar%C3%AE-rxr-synergism-potentiates-retinoid-responsiveness-in-cutaneous-t-cell-lymphoma-cell-lines
#5
Lei Wang, Sebastian S DeMarco, Mary Stuart Peaks, Abigail L Maiorana-Boutilier, JianMing Chen, Miranda J Crouch, Brian M Shewchuk, Saame Raza Shaikh, Charles M Phillips, Lance C Bridges
Retinoids, natural and synthetic derivatives of vitamin A, induce cellular changes by activating nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). Although the ability of retinoids to govern gene expression is exploited clinically for cancer therapeutics, the full benefit of retinoid-based strategies is unrealized due to detrimental side effects. Delineating the receptors that prompt cellular outcomes is critical to advancing retinoid-based approaches. Here we identify the receptors that evoke multiple responses in cutaneous T cell lymphoma (CTCL)...
March 31, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28327177/intestinal-t-lymphocyte-homing-is-associated-with-gastric-emptying-and-epithelial-barrier-function-in-critically-ill-a-prospective-observational-study
#6
Christian Greis, Zohal Rasuly, Rolf A Janosi, Lambros Kordelas, Dietrich W Beelen, Tobias Liebregts
BACKGROUND: Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission. METHODS: We conducted a prospective observational study at two tertiary care medical ICUs...
March 22, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28321213/cd161-tconv-and-cd161-treg-share-a-transcriptional-and-functional-phenotype-despite-limited-overlap-in-tcr%C3%AE-repertoire
#7
Chantal L Duurland, Chrysothemis C Brown, Ryan F L O'Shaughnessy, Lucy R Wedderburn
Human regulatory T cells (Treg) are important in immune regulation, but can also show plasticity in specific settings. CD161 is a lectin-like receptor and its expression identifies an effector-like Treg population. Here, we determined how CD161(+) Treg relate to CD161(+) conventional T cells (Tconv). Transcriptional profiling identified a shared transcriptional signature between CD161(+) Tconv and CD161(+) Treg, which is associated with T helper (Th)1 and Th17 cells, and tissue homing, including high expression of gut-homing receptors...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28279965/lower-levels-of-vitamin-a-are-associated-with-increased-gastrointestinal-graft-versus-host-disease-in-children
#8
Dana T Lounder, Pooja Khandelwal, Christopher Dandoy, Sonata Jodele, Michael Grimley, Gregory Wallace, Adam Lane, Cynthia Taggart, Ashley Teusink-Cross, Kelly Lake, Stella M Davies
Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce risk of graft versus host disease through reduced intestinal permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 post-transplant...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/28207301/mucosal-chemokines
#9
Marcela Hernández-Ruiz, Albert Zlotnik
Several chemokines have important functions in mucosal immunity. While there are many chemokines, 4 of them (CCL25, CCL28, CXCL14, and CXCL17) are especially important in mucosal immunity because they are homeostatically expressed in mucosal tissues. Of these, only CCL25 and CCL28 have been widely recognized as mucosal chemokines. In this study, we review the physiology of these chemokines with specific emphasis on their function in mucosal immunity. CCL25 recruits certain important subsets of T cells that express CCR9 to the small intestine...
February 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28184433/randomised-double-blind-placebo-controlled-trial-of-ccr9-targeted-leukapheresis-treatment-of-ulcerative-colitis-patients
#10
Michael Eberhardson, Per Karlén, Ludvig Linton, Petra Jones, Annelie Lindberg, Martina Jones Kostalla, Emma Lindh, Anders Odén, Hans Glise, Ola Winqvist
No abstract text is available yet for this article.
November 2, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28165741/structural-analysis-of-chemokine-receptor-ligand-interactions
#11
Marta Arimont, Shan-Liang Sun, Rob Leurs, Martine Smit, Iwan J P de Esch, Chris de Graaf
This review focuses on the construction and application of structural chemokine receptor models for the elucidation of molecular determinants of chemokine receptor modulation and the structure-based discovery and design of chemokine receptor ligands. A comparative analysis of ligand binding pockets in chemokine receptors is presented, including a detailed description of the CXCR4, CCR2, CCR5, CCR9, and US28 X-ray structures, and their implication for modeling molecular interactions of chemokine receptors with small-molecule ligands, peptide ligands, and large antibodies and chemokines...
March 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28147349/leukocyte-anti-trafficking-strategies-current-status-and-future-directions
#12
REVIEW
Bruce E Sands
BACKGROUND: In inflammatory bowel diseases (IBD), a pivotal step in the initiation and perpetuation of mucosal inflammation entails the recruitment of inflammatory leukocytes to the gut. Understanding the carefully coordinated series of molecular events that culminate in the recruitment of leukocytes to the gut has resulted in novel interventions with new capabilities in treating both Crohn's disease and ulcerative colitis. Key Messages: Natalizumab, an anti-α4 integrin antibody, was the first agent to demonstrate the efficacy of this approach for the induction and maintenance of response and remission in Crohn's disease...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28101182/protective-effect-of-taraxasterol-against-rheumatoid-arthritis-by-the-modulation-of-inflammatory-responses-in-mice
#13
Shu-Hua Jiang, Li-Feng Ping, Feng-Yan Sun, Xiao-Lei Wang, Zhi-Juan Sun
Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#14
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27898686/gut-homing-cd4-and-cd8-t-cell-frequencies-in-hiv-infected-individuals-on-antiretroviral-treatment
#15
Olivia Briceño, Sandra Pinto-Cardoso, Nataly Rodríguez-Bernabe, Akio Murakami-Ogasawara, Gustavo Reyes-Terán
The depletion of mucosal CD4+ T-cells occurs early in HIV infection and despite years on antiretroviral treatment (ART), this population never reconstitutes to pre-HIV infection levels. In an effort to understand the effect of ART initiation and different ART regimens on the reconstitution of mucosal T cells within the gut associated lymphoid tissue (GALT), we quantified the frequency of CD4+ and CD8+ T cells expressing the gut homing receptors CCR9 and β7 in peripheral blood (PB) of HIV infected individuals naive to ART and treated individuals on both short-term (less than a year) and long-term ART (more than 2 years)...
2016: PloS One
https://www.readbyqxmd.com/read/27892478/continuous-single-cell-imaging-reveals-sequential-steps-of-plasmacytoid-dendritic-cell-development-from-common-dendritic-cell-progenitors
#16
Ezgi Dursun, Max Endele, Andrea Musumeci, Henrik Failmezger, Shu-Hung Wang, Achim Tresch, Timm Schroeder, Anne B Krug
Functionally distinct plasmacytoid and conventional dendritic cells (pDC and cDC) shape innate and adaptive immunity. They are derived from common dendritic cell progenitors (CDPs) in the murine bone marrow, which give rise to CD11c(+) MHCII(-) precursors with early commitment to DC subpopulations. In this study, we dissect pDC development from CDP into an ordered sequence of differentiation events by monitoring the expression of CD11c, MHC class II, Siglec H and CCR9 in CDP cultures by continuous single cell imaging and tracking...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27832135/intestinal-dendritic-cells-are-altered-in-number-maturity-and-chemotactic-ability-in-fulminant-hepatic-failure
#17
Mei Liu, Peng Wang, Min Zhao, D Y Liu
Fulminant hepatic failure (FHF) is defined as rapid acute liver injury, often complicated with spontaneous bacterial peritonitis (SBP). The precise onset of FHF with SBP is still unknown, but it is thought that SBP closely correlates with a weakened intestinal barrier. Dendritic cells (DCs) play a crucial role in forming the intestinal immune barrier, therefore the number, maturity and chemotactic ability of intestinal DCs were studied in FHF. Mouse intestinal and spleen DCs were isolated by magnetic-activated cell sorting (MACS) and surface markers of DCs, namely CD11c, CD74, CD83 and CD86, were identified using flow cytometry...
2016: PloS One
https://www.readbyqxmd.com/read/27829595/imiquimod-induced-ccr9-ameliorates-murine-tnbs-colitis
#18
Ryoma Suzuki, Kyoko Katakura, Tatsuo Fujiwara, Naohiko Gunji, Hiroshi Watanabe, Hiromasa Ohira
To investigate whether Imiquimod (IMQ) as TLR7 ligand protects mice from colonic inflammation and the mechanisms underlying in such immunoregulatory conditions. METHODS: Murine colitis was induced to Balb/c mice by administration of trinitrobenzene sulfonic acid (TNBS) with or without daily intraperitoneal administration of IMQ. Colitis was evaluated by body weight decreases and by histological score. Also colonic mRNA expression was measured by RT-PCR. To confirm the induction of Regulatory T cells (Tregs) by type-1 IFN from pDCs, we generated mouse bone marrow-derived pDCs and co-cultured these with CD4(+) T cells isolated from mouse spleen with or without IMQ stimulation...
December 16, 2016: Fukushima Journal of Medical Science
https://www.readbyqxmd.com/read/27807000/randomized-double-blind-placebo-controlled-trial-of-ccr9-targeted-leukapheresis-treatment-of-ulcerative-colitis-patients
#19
Michael Eberhardson, Per Karlén, Ludvig Linton, Petra Jones, Annelie Lindberg, Martina Jones Kostalla, Emma Lindh, Anders Odén, Hans Glise, Ola Winqvist
BACKGROUND AND AIMS: Ulcerative colitis patients display increased number of circulating pro-inflammatory HLA-DR(hi) monocytes expressing high levels of the gut homing chemokine receptor CCR9 and TNF-α. The aim of this first-in-man double blind randomized placebo controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis with regards to safety, tolerability and immunological response...
November 2, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/27795621/ccr9-is-a-key-regulator-of-early-phases-of-allergic-airway-inflammation
#20
C López-Pacheco, G Soldevila, G Du Pont, R Hernández-Pando, E A García-Zepeda
Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes...
2016: Mediators of Inflammation
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