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https://www.readbyqxmd.com/read/29348563/disruption-of-cxcr3-function-impedes-the-development-of-sj%C3%A3-gren-s-syndrome-like-xerostomia-in-non-obese-diabetic-mice
#1
Jing Zhou, Qing Yu
The chemokine receptor CXCR3 plays an important role in T cell recruitment in various immune responses and autoimmune diseases. Expression of CXCR3 ligands, including CXCL9, CXCL10, and CXCL11, is elevated in the salivary glands of patients with Sjögren's syndrome (SS). To elucidate whether interaction between CXCR3 and its ligands is required for the development of SS, we administrated an anti-CXCR3 blocking antibody (CXCR3-173) to the non-obese diabetic (NOD) mice, a well-defined model of SS, during the stage prior to disease onset...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29343553/molecular-mechanisms-of-biased-and-probe-dependent-signaling-at-cxcr3-induced-by-negative-allosteric-modulators
#2
Regine Brox, Lampros Milanos, Noureldin Saleh, Paul Baumeister, Armin Buschauer, Dagmar Hofmann, Markus R Heinrich, Timothy Clark, Nuska Tschammer
Our recent explorations of allosteric modulators (AMs) with improved properties resulted in the identification of two biased negative AMs, N-1-{[3-(4-Ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimi-din2yl]ethyl}-4-(4-fluorobutoxy)-N-[(1-methylpiperidin-4-yl)me-thyl}]butanamide (BD103) and {5-[(N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamido)methyl]-2-fluorophenyl}boronic acid (BD064), that exhibited probe-dependent inhibition of the chemokine receptor CXCR3 signaling...
January 17, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29338773/chemokine-ligand-receptor-interactions-critically-regulate-cutaneous-wound-healing
#3
Erich Bünemann, Norman-Philipp Hoff, Bettina Alexandra Buhren, Ulrike Wiesner, Stephan Meller, Edwin Bölke, Anja Müller-Homey, Robert Kubitza, Thomas Ruzicka, Albert Zlotnik, Bernhard Homey, Peter Arne Gerber
BACKGROUND: Wound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders...
January 16, 2018: European Journal of Medical Research
https://www.readbyqxmd.com/read/29316433/tim-3-regulates-cd103-dendritic-cell-function-and-response-to-chemotherapy-in-breast-cancer
#4
Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S Rugo, Matthew F Krummel, Lisa M Coussens, Brian Ruffell
Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29315893/mechanisms-regulating-expansion-of-cd8-t-cells-during-hiv-1-infection
#5
REVIEW
A Nasi, F Chiodi
Abnormal immune activation and expansion of CD8+ T cells, especially of memory and effector phenotypes, take place during HIV-1 infection, and these abnormal features persist during administration of antiretroviral therapy (ART) to infected patients. The molecular mechanisms for CD8+ T-cell expansion remain poorly characterized. In this article, we review the literature addressing features of CD8+ T-cell immune pathology and present an integrated view on the mechanisms leading to abnormal CD8+ T-cell expansion during HIV-1 infection...
January 5, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29302252/serosal-cavities-contain-two-populations-of-innate-like-integrin-%C3%AE-4highcd4-t-cells-integrin-%C3%AE-4%C3%AE-1-%C3%AE-6%C3%AE-1-%C3%AE-4%C3%AE-7-and-%C3%AE-4%C3%AE-1-%C3%AE-6%C3%AE-1-%C3%AE-4%C3%AE-7-cells
#6
Jeong In Yang, Chanho Park, Inseong Kho, Sujin Lee, Kyung-Suk Suh, Tae Jin Kim
We previously reported peritoneal innate-like integrin α4 (CD49d)highCD4+ T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin α4highCD4+ T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin α4highCD4+ T cells to integrin α4lowCD4+ T cells than peritoneal cavity, but the pleural integrin α4highCD4+ T cells have the same characteristics of the peritoneal integrin α4highCD4+ T cells...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29301792/therapy-educated-mesenchymal-stem-cells-enrich-for-tumor-initiating-cells
#7
Michael Timaner, Nitzan Letko-Khait, Ruslana Kotsofruk, Madeleine Benguigui, Ofrat Beyar-Katz, Chen Rachman-Tzemach, Ziv Raviv, Tomer Bronshtein, Marcelle Machluf, Yuval Shaked
Stromal cells residing in the tumor microenvironment contribute to the development of therapy resistance. Here we show that chemotherapy-educated mesenchymal stem cells (MSCs) promote therapy resistance via crosstalk with tumor-initiating cells (TICs), a resistant tumor cell subset that initiates tumorigenesis and metastasis. In response to gemcitabine chemotherapy, MSCs colonized pancreatic adenocarcinomas in large numbers and resided in close proximity to TICs. Furthermore, gemcitabine-educated MSCs promoted the enrichment of TICs in vitro and enhance tumor growth in vivo...
January 4, 2018: Cancer Research
https://www.readbyqxmd.com/read/29297451/cxcr3-ligands-in-pleural-fluid-as-markers-for-the-diagnosis-of-tuberculous-pleural-effusion
#8
W Chung, Y Jung, K Lee, J Park, S Sheen, K Park
SETTING: A tertiary care academic medical centre. OBJECTIVE: To evaluate the clinical usefulness of C-X-C motif chemokine receptor 3 (CXCR3) ligands in tuberculous pleural effusion (TPE). DESIGN: We recruited 336 patients with pleural effusion due to various causes. Concentrations of interferon-gamma (IFN-γ) and the CXCR3 ligands CXCL9 and CXCL11 were determined using enzyme immunoassays; adenosine deaminase (ADA) activity was measured in pleural fluid and serum...
December 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#9
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29288898/cxcr3-blockade-combined-with-cyclosporine-a-alleviates-acute-graft-versus-host-disease-by-inhibiting-alloreactive-donor-t-cell-responses-in-a-murine-model
#10
Shengchao Miao, Bo Tang, Huihui Liu, Zhenhua Wang, Yongjin Shi, Yujun Dong, Wei Liu, Chenchen Qin, Hanyun Ren
Chemotaxis of T cells to acute graft-versus-host disease (aGvHD) target tissues directed by chemokines and their receptors plays a key role in the pathogenesis of aGvHD. Blockade of lymphocyte migration by targeting chemokine receptors may be a viable strategy for the prevention and treatment of aGvHD, which is quite distinguishable from typical efforts to use immunosuppressive medications that have been associated with some side effects. CXCR3 and its ligands have been reported to be correlated with aGvHD pathogenesis...
December 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29288198/the-chemokine-receptor-cxcr3-promotes-cd8-t-cell-accumulation-in-uninfected-salivary-glands-but-is-not-necessary-after-murine-cytomegalovirus-infection
#11
Sofia Caldeira-Dantas, Thomas Furmanak, Corinne Smith, Michael Quinn, Leyla Y Teos, Adam Ertel, Drishya Kurup, Mayank Tandon, Ilias Alevizos, Christopher M Snyder
Recent work indicates that salivary glands are able to constitutively recruit CD8+ T cells and retain them as tissue-resident memory T cells, independently of local infection, inflammation, or Ag. To understand the mechanisms supporting T cell recruitment to the salivary gland, we compared T cell migration to the salivary gland in mice that were infected or not with murine CMV (MCMV), a herpesvirus that infects the salivary gland and promotes the accumulation of salivary gland tissue-resident memory T cells...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29287991/t-cell-phenotypes-in-women-with-chlamydia-trachomatis-infection-and-influence-of-treatment-on-phenotype-distributions
#12
Brian M O Ogendi, Rakesh K Bakshi, Kanupriya Gupta, Richa Kapil, LaDraka T Brown, Stephen J Jordan, Steffanie Sabbaj, Christen G Press, Jeannette Y Lee, William M Geisler
T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38+HLA-DR+), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3+CCR5+ and CCR4+, respectively), and T cell homing marker (CCR7) for both CD4+ and CD8+ T cells in CT-infected women...
December 26, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29286143/epithelial-mesenchymal-transition-induced-by-the-cxcl9-cxcr3-axis-through-akt-activation-promotes-invasion-and-metastasis-in-tongue-squamous-cell-carcinoma
#13
Ziliang Li, Jianqi Liu, Lei Li, Shuai Shao, Jianhua Wu, Li Bian, Yongwen He
The present study aimed to assess the induction of epithelial-mesenchymal transition (EMT), invasion, and metastasis by the chemokine CXCL9/receptor CXCR3 axis in tongue squamous cell carcinoma (TSCC), unveiling the underlying mechanisms and providing new insights into the prevention and treatment of oral cancer metastasis. The expression levels of CXCL9 and CXCR3 in TSCC tissue specimens were determined by immunohistochemistry, assessing differences between samples with cervical lymph node metastasis and those without...
December 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29282904/human-t-cell-responses-to-dengue-and-zika-virus-infection-compared-to-dengue-zika-coinfection
#14
Jessica Badolato-Corrêa, Juan Camilo Sánchez-Arcila, Thiara Manuele Alves de Souza, Luciana Santos Barbosa, Priscila Conrado Guerra Nunes, Monique da Rocha Queiroz Lima, Mariana Gandini, Ana Maria Bispo de Filippis, Rivaldo Venâncio da Cunha, Elzinandes Leal de Azeredo, Luzia Maria de-Oliveira-Pinto
INTRODUCTION: Zika virus (ZIKV) and dengue virus (DENV) co-circulated during latest outbreaks in Brazil, hence, it is important to evaluate the host cross-reactive immune responses to these viruses. So far, little is known about human T cell responses to ZIKV and no reports detail adaptive immune responses during DENV/ZIKV coinfection. METHODS: Here, we studied T cells responses in well-characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV-exposed healthy donors...
December 28, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29281764/interferon-regulatory-factor-1-is-essential-for-pathogenic-cd8-t-cell-migration-and-retention-in-the-brain-during-experimental-cerebral-malaria
#15
Sin Yee Gun, Carla Claser, Teck Hui Teo, Shanshan W Howland, Chek Meng Poh, Rebecca Ren Ying Chye, Lisa F P Ng, Laurent Rénia
Host immune response has a key role in controlling the progression of malaria infection. In the well-established murine model of experimental cerebral malaria (ECM) with P. berghei ANKA infection, pro-inflammatory Th1 and CD8+ T cells response are essential for disease development. Interferon regulatory factor 1 (IRF1) is a transcription factor which promotes Th1 responses and its absence was previously shown to protect from ECM death. Yet, the exact mechanism of protection remains unknown. Here we demonstrated that IRF1-deficient mice (IRF1KO) were protected from ECM death despite displaying early neurological signs...
December 27, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29277541/hpv16e7-induced-hyperplasia-promotes-cxcl9-10-expression-and-induces-cxcr3-t-cell-migration-to-skin
#16
Paula Kuo, Zewen K Tuong, Siok Min Teoh, Ian H Frazer, Stephen Mattarollo, Graham R Leggatt
Chemokines regulate tissue immunity by recruiting specific subsets of immune cells. Mice expressing the E7 protein of HPV16 as a transgene from a keratin 14 promoter (K14.E7) show increased epidermal and dermal lymphocytic infiltrates, epidermal hyperplasia and suppressed local immunity. Here, we show that CXCL9 and CXCL10 are overexpressed in non-haematopoietic cells in skin of K14.E7 mice when compared with non-transgenic animals, and recruit CXCR3+ lymphocytes to the hyperplastic skin. Overexpression of CXCL9 and CXCL10 is not observed in E7 transgenic mice with mutated Rb gene whose protein product cannot interact with E7 (K14...
December 22, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29251019/the-ror%C3%AE-t-ccr6-ccl20-axis-augments-th17-cells-invasion-into-the-synovia-of-rheumatoid-arthritis-patients
#17
Shunta Kaneko, Yuya Kondo, Masahiro Yokosawa, Kotona Furuyama, Seiji Segawa, Hiroto Tsuboi, Akihiro Kanamori, Isao Matsumoto, Masashi Yamazaki, Takayuki Sumida
OBJECTIVES: To clarify the pathogenic role of transcription factor expression of CD4+ T helper (Th) cell subsets in the development of rheumatoid arthritis (RA). METHODS: We collected CD4+ T cells from peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) by magnetic cell sorting. The proportion of Th cell subsets were classified from cell surface markers (CD45RA, CXCR5, CXCR3, CCR6) and the expression of their transcription factors (T-bet, GATA3, RORγt) were analyzed by flow cytometry before and at 24 weeks after anti-rheumatic treatment...
December 18, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/29248547/dual-role-of-ezh2-in-cutaneous-anaplastic-large-cell-lymphoma-promoting-tumor-cell-survival-and-regulating-tumor-microenvironment
#18
Shengguo Yi, Jingru Sun, Lei Qiu, Wenjing Fu, Anqi Wang, Xiaoqing Liu, Yong Yang, Marshall E Kadin, Ping Tu, Yang Wang
Primary cutaneous anaplastic T cell lymphoma (PCALCL), characterized by the CD30+ anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma (CTCL). Little is known about the mechanisms of disease progression. Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation (H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL...
December 14, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29239897/ex-vivo-expression-of-chemokine-receptors-on-cells-surrounding-cutaneous-nerves-in-patients-with-hiv-associated-sensory-neuropathy
#19
Jenjira Mountford, Fitri Octaviana, Riwanti Estiasari, Denise Dewanto Setiawan, Ibnu Ariyanto, Silvia Lee, Jessica Gaff, Constance Chew, Connie Jackaman, Peter Kamerman, Catherine Cherry, Patricia Price
OBJECTIVE: HIV-associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving anti-retroviral therapy (ART), even though neurotoxic anti-retroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesise that chemokines produced locally in the skin promote migration of macrophages and T-cells into the tissue, damaging cutaneous nerves causing HIV-SN. DESIGN: We assessed chemokine receptor expression on infiltrating CD14 and CD3 cells around cutaneous nerves in standardised skin biopsies from HIV-SN+ patients (n = 5), HIV-SN- patients (n = 9) and healthy controls (n = 4)...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29236760/distribution-of-circulating-t-follicular-helper-cell-subsets-is-altered-in-immunoglobulin-a-vasculitis-in-children
#20
Deying Liu, Jinxiang Liu, Jinghua Wang, Lishuang Guo, Congcong Liu, Yanfang Jiang, Haifeng Wang, Sirui Yang
BACKGROUND: Immunoglobulin A vasculitis (IgAV) is the most common vasculitis in children. Previously, we demonstrated that patients with IgAV show abnormal proliferation of cluster of differentiation (CD)4+C-X-C chemokine receptor type (CXCR)5+ follicular helper T (Tfh) cells. Here, we explored the status of Tfh cell subsets and plasma cytokine levels in patients with IgAV. METHODS: CD4+CXCR5+CD45RA-, CD45RA-CXCR3+CCR6-, CD45RA-CXCR3-CCR6-, CD45RA-CXCR3-CCR6+, and CD45RA-CXCR3+CCR6+ Tfh cell fractions and plasma concentrations of interferon-γ, interleukin (IL)-4, and IL-17A were evaluated by flow cytometry and a flow cytometric bead array, respectively, in 30 patients with IgAV and 15 healthy controls (HCs)...
2017: PloS One
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