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https://www.readbyqxmd.com/read/27895171/impairment-of-ccr6-and-cxcr3-th-cell-migration-in-hiv-1-infection-is-rescued-by-modulating-actin-polymerization
#1
Valentina Cecchinato, Enos Bernasconi, Roberto F Speck, Michele Proietti, Ulrike Sauermann, Gianluca D'Agostino, Gabriela Danelon, Tanja Rezzonico Jost, Fabio Grassi, Lorenzo Raeli, Franziska Schöni-Affolter, Christiane Stahl-Hennig, Mariagrazia Uguccioni
CD4(+) T cell repopulation of the gut is rarely achieved in HIV-1-infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6(+) and CXCR3(+) Th cells accumulate in the blood of aviremic HIV-1-infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27886644/oral-administration-with-diosgenin-enhances-the-induction-of-intestinal-t-helper-1-like-regulatory-t-cells-in-a-murine-model-of-food-allergy
#2
Chung-Hsiung Huang, Chia-Chi Wang, Yu-Jin Lin, Masatoshi Hori, Tong-Rong Jan
Although the development of T helper (Th)1-like regulatory T (Treg) cells under Th1 inflammatory conditions has been reported, the role of Th1-like Treg cells in Th2 allergic responses remains mostly unclear. We previously demonstrated that diosgenin, the major sapogenin contained in the Chinese yam, attenuated food allergy and augmented Th1 and Treg immune responses. In this study, we hypothesized that diosgenin may enhance the induction of Th1-like Treg cells in the gut of mice with food allergy. Ovalbumin (OVA)-sensitized BALB/c mice were gavaged daily with diosgenin and received repeatedly intragastric ovalbumin challenges to induce intestinal allergic responses...
November 22, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27879287/tissue-specific-programming-of-memory-cd8-t-cell-subsets-impacts-protection-against-lethal-respiratory-virus-infection
#3
Georges Abboud, Pritesh Desai, Farhad Dastmalchi, Jessica Stanfield, Vikas Tahiliani, Tarun E Hutchinson, Shahram Salek-Ardakani
How tissue-specific anatomical distribution and phenotypic specialization are linked to protective efficacy of memory T cells against reinfection is unclear. Here, we show that lung environmental cues program recently recruited central-like memory cells with migratory potentials for their tissue-specific functions during lethal respiratory virus infection. After entering the lung, some central-like cells retain their original CD27(hi)CXCR3(hi) phenotype, enabling them to localize near the infected bronchiolar epithelium and airway lumen to function as the first line of defense against pathogen encounter...
November 22, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27878235/accelerated-cell-cycle-progression-of-human-regulatory-t%C3%A2-cell-like-cell-line-caused-by-continuous-exposure-to-asbestos-fibers
#4
Suni Lee, Hidenori Matsuzaki, Megumi Maeda, Shoko Yamamoto, Naoko Kumagai-Takei, Tamayo Hatayama, Miho Ikeda, Kei Yoshitome, Yasumitsu Nishimura, Takemi Otsuki
Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma...
November 22, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27875312/mutational-analysis-of-atypical-chemokine-receptor-3-ackr3-cxcr7-interaction-with-its-chemokine-ligands-cxcl11-and-cxcl12
#5
Besma Benredjem, Mélanie Girard, David Rhainds, Geneviève St-Onge, Nikolaus Heveker
Atypical chemokine receptors do not mediate chemotaxis or G-protein signalling, but they recruit arrestin. They also efficiently scavenge their chemokine ligands, thereby contributing to gradient maintenance and termination. ACKR3, also known as CXCR7, binds and degrades the constitutive chemokine CXCL12, which also binds the canonical receptor CXCR4, and CXCL11, which also binds CXCR3. Here we report comprehensive mutational analysis of the ACKR3 interaction with its chemokine ligands, using 30 substitution mutants...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27872865/cxcr3-ccr5-and-crth2-chemokine-receptor-expression-in-lymphocytes-infiltrating-thyroid-nodules-with-coincident-hashimoto-s-thyroiditis-obtained-by-fine-needle-aspiration-biopsy
#6
Jan Jiskra, Marie Antošová, Jan Krátký, Hana Vítková, Zdeňka Límanová, Helena Marečková, Eliška Potluková
Objective. To determine the expression of chemokine receptors in lymphocytes from thyroid nodules and peripheral blood in patients with and without Hashimoto's thyroiditis (HT). Patients and Methods. The study included 46 women with thyroid nodules and HT and 60 women with thyroid nodules without HT (controls) who underwent a fine needle aspiration biopsy (FNAB). Expression of chemokine receptors CXCR3, CCR5, and CRTH2 was assessed by flow cytometry in lymphocytes from FNAB samples and from peripheral blood...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27872297/singular-role-for-t-bet-cxcr3-regulatory-t-cells-in-protection-from-autoimmune-diabetes
#7
Tze Guan Tan, Diane Mathis, Christophe Benoist
Foxp3(+) regulatory T (Treg) cells are crucial for restraining inflammation in a variety of autoimmune diseases, including type 1 diabetes (T1D). However, the transcriptional and functional phenotypes of Treg cells within the pancreatic lesion remain poorly understood. Here we characterized pancreas-infiltrating Treg cells in the NOD mouse model of T1D and uncovered a substantial enrichment of the Treg subpopulation expressing the chemokine receptor CXCR3. Accumulation of CXCR3(+) Treg cells within pancreatic islets was dependent on the transcription factor T-BET, and genetic ablation of T-BET increased the onset and penetrance of disease, abrogating the sex bias normally seen in the NOD model...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27870968/the-cardiac-maladaptive-atf3-dependent-cross-talk-between-cardiomyocytes-and-macrophages-is-mediated-by-the-ifn%C3%AE-cxcl10-cxcr3-axis
#8
L Koren, U Barash, Y Zohar, N Karin, A Aronheim
RATIONAL: Pressure overload induces adaptive and maladaptive cardiac remodeling processes in the heart. Part of the maladaptive process is the cross-talk between cardiomyocytes and macrophages which is dependent on the function of the Activating Transcription Factor 3, ATF3. Yet, the molecular mechanism involved in cardiomyocytes-macrophages communication leading to macrophages recruitment to the heart and cardiac maladaptive remodeling is currently unknown. METHODS AND RESULTS: Isolated peritoneal macrophages from either wild type or ATF3-KO mice were cultured in serum free medium to collect conditioned medium (CM)...
November 10, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27865203/minocycline-prevents-cerebral-malaria-confers-neuroprotection-and-increases-survivability-of-mice-during-plasmodium-berghei-anka-infection
#9
Thittayil Suresh Apoorv, Phanithi Prakash Babu
Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study...
November 16, 2016: Cytokine
https://www.readbyqxmd.com/read/27862735/identification-of-two-distinct-sites-for-antagonist-and-biased-agonist-binding-to-the-human-chemokine-receptor-cxcr3
#10
Lampros Milanos, Noureldin Saleh, Ralf C Kling, Jonas Kaindl, Nuska Tschammer, Timothy Clark
The chemokine receptor CXCR3 is a G protein-coupled receptor that conveys extracellular signals into cells by changing its conformation upon ligand binding. We previously hypothesized that small-molecule allosteric CXCR3-agonists do not bind to the same allosteric binding pocket as 8-azaquinazolinone-based negative allosteric modulators. We have now performed molecular-dynamics (MD) simulations with metadynamics enhanced sampling on the CXCR3 system to refine structures and binding modes and to predict the CXCR3-binding affinities of the biased allosteric agonist FAUC1036 and the negative allosteric modulator RAMX3...
November 9, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27828999/cxcl4-and-cxcl4l1-differentially-affect-monocyte-survival-and-dendritic-cell-differentiation-and-phagocytosis
#11
Mieke Gouwy, Pieter Ruytinx, Egle Radice, Federico Claudi, Katrien Van Raemdonck, Raffaella Bonecchi, Massimo Locati, Sofie Struyf
Upon inflammation, circulating monocytes leave the bloodstream and migrate into the tissues, where they differentiate after exposure to various growth factors, cytokines or infectious agents. The best defined macrophage polarization types are M1 and M2. However, the platelet-derived CXC chemokine CXCL4 induces the polarization of macrophages into a unique phenotype. In this study, we compared the effect of CXCL4 and its variant CXCL4L1 on the differentiation of monocytes into macrophages and into immature monocyte-derived dendritic cells (iMDDC)...
2016: PloS One
https://www.readbyqxmd.com/read/27816291/atrophying-pityriasis-versicolor-as-an-idiosyncratic-t%C3%A2-cell-mediated-response-to-malassezia-a-case-series
#12
Jonathan Michael Stephen Levy, Cynthia Magro
BACKGROUND: Atrophying pityriasis versicolor (PV), first described in 1971, is a rare variant in which lesions appear atrophic. OBJECTIVE: We sought to determine the pathophysiology of atrophying PV. METHODS: A retrospective chart review identified 6 cases of atrophying PV. In all cases, routine light microscopy, an elastic tissue stain, and immunohistochemical assessment for the expression of CD3, CD4, CD8, GATA3 and CXCR3 was performed. RESULTS: All cases demonstrated hyperkeratosis with intracorneal infiltration by pathogenic hyphal forms as well as epidermal attenuation and papillary dermal elastolysis...
November 2, 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27800533/natalizumab-treatment-leads-to-an-increase-in-circulating-cxcr3-expressing-b-cells
#13
Maija Saraste, Tarja-Leena Penttilä, Laura Airas
OBJECTIVE: To study the effects of natalizumab treatment on subgroups of circulating peripheral blood B cell populations. METHODS: We studied the proportions and absolute numbers of CD19(+)CD20(+), CD10(+), and CD5(+) B cell populations, and determined very late activation antigen-4 and chemokine receptor CXCR3, CCR5, and CCR6 expression on B cells in the peripheral blood of 14 natalizumab-treated patients with relapsing-remitting multiple sclerosis. Five blood samples per patient were obtained longitudinally before and during the first year of treatment...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27799622/pmhc-affinity-controls-duration-of-cd8-t-cell-dc-interactions-and-imprints-timing-of-effector-differentiation-versus-expansion
#14
Aleksandra J Ozga, Federica Moalli, Jun Abe, Jim Swoger, James Sharpe, Dietmar Zehn, Mario Kreutzfeldt, Doron Merkler, Jorge Ripoll, Jens V Stein
During adaptive immune responses, CD8(+) T cells with low TCR affinities are released early into the circulation before high-affinity clones become dominant at later time points. How functional avidity maturation is orchestrated in lymphoid tissue and how low-affinity cells contribute to host protection remains unclear. In this study, we used intravital imaging of reactive lymph nodes (LNs) to show that T cells rapidly attached to dendritic cells irrespective of TCR affinity, whereas one day later, the duration of these stable interactions ceased progressively with lowering peptide major histocompatibility complex (pMHC) affinity...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27795961/the-cxcl10-cxcr3-axis-and-cardiac-inflammation-implications-for-immunotherapy-to-treat-infectious-and-noninfectious-diseases-of-the-heart
#15
REVIEW
Raffaele Altara, Ziad Mallat, George W Booz, Fouad A Zouein
Accumulating evidence reveals involvement of T lymphocytes and adaptive immunity in the chronic inflammation associated with infectious and noninfectious diseases of the heart, including coronary artery disease, Kawasaki disease, myocarditis, dilated cardiomyopathies, Chagas, hypertensive left ventricular (LV) hypertrophy, and nonischemic heart failure. Chemokine CXCL10 is elevated in cardiovascular diseases, along with increased cardiac infiltration of proinflammatory Th1 and cytotoxic T cells. CXCL10 is a chemoattractant for these T cells and polarizing factor for the proinflammatory phenotype...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27789141/ii-discovery-of-a-novel-series-of-cxcr3-antagonists-with-a-beta-amino-acid-core
#16
Imre Bata, Zsuzsanna Tömösközi, Péter Buzder-Lantos, Attila Vasas, Gábor Szeleczky, László Balázs, Veronika Barta-Bodor, György G Ferenczy
A new series of beta amino acids, which act as CXCR3 antagonists, has been identified. The formerly optimized N,N-disubstituted benzylamine derivatives with carboxylic acid function on the N-atom was used as starting point and compounds with carboxyl function not attached to the N-atom were investigated. Affinity, metabolic stability in human and mouse liver microsomes and Caco-2 permeability were optimized. Compounds with double-digit nanomolar CXCR3 affinity, favourable microsomal stability and Caco-2 permeability have been identified...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27789137/i-discovery-of-a-novel-series-of-cxcr3-antagonists-multiparametric-optimization-of-n-n-disubstituted-benzylamines
#17
Imre Bata, Zsuzsanna Tömösközi, Péter Buzder-Lantos, Attila Vasas, Gábor Szeleczky, Sándor Bátori, Veronika Barta-Bodor, László Balázs, György G Ferenczy
N,N-Disubstituted benzylamine derivatives have been identified as CXCR3 antagonists. Compounds were optimized to improve affinity and selectivity, to increase metabolic stability in human and mouse liver microsomes, to increase Caco-2 permeability. Optimization was supported by monitoring physico-chemical properties using both experimental and computational means. Several compounds with double-digit nanomolar CXCR3 affinity, favorable selectivity, microsomal stability, Caco-2 permeability and human hepatocyte clearance have been identified...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27776524/pulsed-high-dose-dexamethasone-modulates-th1-th2-chemokine-imbalance-in-immune-thrombocytopenia
#18
Zongtang Liu, Meiying Wang, Shufen Zhou, Ji Ma, Yan Shi, Jun Peng, Ming Hou, Chengshan Guo
BACKGROUND: Chemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways. METHODS: Th1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied...
October 24, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27769508/b-lymphopoiesis-in-fetal-liver-guided-by-chemokines
#19
K Kajikhina, M Tsuneto, F Melchers
Early in embryonic development of mice, from day 12.5 after conception, myeloid-lymphoid bipotent progenitors, expressing receptors both for IL7 and CSF-1, migrate from embryonic blood into developing fetal liver. These progenitors also express multiple chemokine receptors, i.e., CCR7, CXCR3, CXCR4, and CXCR5, all on one cell. Their migration through LYVE-1+ vascular endothelium is guided by CCR7, recognizing the chemokine CCL19, and by CXCR3, recognizing CXCL10/11, chemokines which are both produced by the endothelium...
2016: Advances in Immunology
https://www.readbyqxmd.com/read/27766097/dysregulation-of-chemokine-chemokine-receptor-axes-and-nk-cell-tissue-localization-during-diseases
#20
Giovanni Bernardini, Fabrizio Antonangeli, Valentina Bonanni, Angela Santoni
Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signaling via their specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process...
2016: Frontiers in Immunology
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