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https://www.readbyqxmd.com/read/28207301/mucosal-chemokines
#1
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
#2
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
#3
Marta Arimont, Shanliang 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...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28147349/leukocyte-anti-trafficking-strategies-current-status-and-future-directions
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27795503/role-of-inflammatory-macrophages-and-ccr9-ccl25-chemokine-axis-in-the-pathogenesis-of-liver-injury-as-a-therapeutic-target
#13
Nobuhiro Nakamoto
  It is widely known that a variety of immune cells in the liver contribute to the pathogenesis of liver diseases. Recently, roles of chemokines/chemokines receptors axes regarding the migration of immune competent cells to the inflamed liver have been reported as possible therapeutic targets. We here showed that CCR9(+) CD11b(+) macrophages play an important role during the course of Concanavalin A-induced murine acute liver injury as well as human acute hepatitis via the production of inflammatory cytokines and the Th1 induction...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27766171/tissue-specific-induction-of-ccr6-and-nrp1-during-early-cd4-t-cell-differentiation
#14
Joern Pezoldt, Jochen Huehn
Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α4β7, both required for migration of effector T cells into mucosal tissues...
September 29, 2016: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/27733581/the-tnf-family-member-tl1a-induces-il-22-secretion-in-committed-human-th17-cells-via-il-9-induction
#15
Lisa S Thomas, Stephan R Targan, Masato Tsuda, Qi T Yu, Brenda C Salumbides, Talin Haritunians, Emebet Mengesha, Dermot P B McGovern, Kathrin S Michelsen
TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those of the bowel by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong costimulation of these TH subsets, particularly of mucosal CCR9(+) T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. We investigated the function of TL1A on human TH17 cells. TL1A, together with TGF-β, IL-6, and IL-23, enhanced the secretion of IL-17 and IFN-γ from human CD4(+) memory T cells...
October 12, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27725760/bone-marrow-derived-macrophages-distinct-from-tissue-resident-macrophages-play-a-pivotal-role-in-concanavalin-a-induced-murine-liver-injury-via-ccr9-axis
#16
Takeru Amiya, Nobuhiro Nakamoto, Po-Sung Chu, Toshiaki Teratani, Hideaki Nakajima, Yumi Fukuchi, Nobuhito Taniki, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Hirotoshi Ebinuma, Takanori Kanai
The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9(+) inflammatory Mφs play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9(+)Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding...
October 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27693537/resveratrol-treatment-attenuates-chemokine-receptor-expression-in-the-btbr-t-tf-j-mouse-model-of-autism
#17
Saleh A Bakheet, Mohammad Zeed Alzahrani, Ahmed Nadeem, Mushtaq Ahmad Ansari, Khairy M A Zoheir, Sabry M Attia, Laila Yousef Al-Ayadhi, Sheikh Fayaz Ahmad
Autism is a neurodevelopmental disorder categorized by qualitative impairments in social interaction, communication, and repetitive stereotypic behavior. Emerging evidence increasingly suggests that chemokine receptors have a pivotal role in the central nervous system and are involved in the pathogenesis of numerous neuroinflammatory diseases. Resveratrol is widely used to treat neurodegenerative diseases, but its effect on autism has not been investigated. We investigated the effect of resveratrol (20 and 40mg/kg) in the spleen and brain tissues of BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice as well as on the C-C chemokine receptor (CCR) and C-X-C motif chemokine receptor (CXCR) (CCR3(+), CCR5(+), CCR7(+) and CCR9(+), CXCR3(+) and CXCR5(+)) in cluster of differentiation 4-positive (CD4(+)) T cells in the spleen...
December 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27596266/limited-clonal-relatedness-between-gut-iga-plasma-cells-and-memory-b-cells-after-oral-immunization
#18
Mats Bemark, Helena Hazanov, Anneli Strömberg, Rathan Komban, Joel Holmqvist, Sofia Köster, Johan Mattsson, Per Sikora, Ramit Mehr, Nils Y Lycke
Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8(high)/GFP(+) NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured...
2016: Nature Communications
https://www.readbyqxmd.com/read/27589591/oral-vaccination-with-attenuated-salmonella-typhimurium-delivered-tspmy-dna-vaccine-elicits-protective-immunity-against-trichinella-spiralis-in-balb-c-mice
#19
Lei Wang, Xiaohuan Wang, Kuo Bi, Ximeng Sun, Jing Yang, Yuan Gu, Jingjing Huang, Bin Zhan, Xinping Zhu
BACKGROUND: Our previous studies showed that Trichinella spiralis paramyosin (TsPmy) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack. Vaccination with recombinant TsPmy protein induced protective immunity against T. spiralis larval challenge. Due to the difficulty in producing TsPmy as a soluble recombinant protein, we prepared a DNA vaccine as an alternative approach in order to elicit a robust immunity against Trichinella infection...
September 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27585634/abrogation-of-cc-chemokine-receptor-9-ameliorates-ventricular-remodeling-in-mice-after-myocardial-infarction
#20
Yan Huang, Dandan Wang, Xin Wang, Yijie Zhang, Tao Liu, Yuting Chen, Yanhong Tang, Teng Wang, Dan Hu, Congxin Huang
CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism...
2016: Scientific Reports
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