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https://www.readbyqxmd.com/read/28624449/intratumoral-injection-of-ifn-%C3%AE-induces-chemokine-production-in-melanoma-and-augments-the-therapeutic-efficacy-of-anti-pd-l1-mab
#1
Jiro Uehara, Takayuki Ohkuri, Akemi Kosaka, Kei Ishibashi, Yui Hirata, Kenzo Ohara, Toshihiro Nagato, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Akemi Ishida-Yamamoto, Hiroya Kobayashi
Despite recent advances in treatment for melanoma patients through using immune checkpoint inhibitors, these monotherapies have limitations and additional treatments have been explored. Type I IFNs have been used to treat melanoma and possess immunomodulatory effects including enhancement of T-cell infiltration. T-cell plays a critical role in immune checkpoint therapies via restoration of effector functions and tumor infiltration by T-cells predicts longer survival in a variety of cancer types. Moreover, tumor-infiltrating T-cells are associated with the expression of chemokines such as CCL5 and CXCR3 ligands in tumor tissues...
June 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28623423/cxcl10-suppression-of-hem-and-lymph-angiogenesis-in-inflamed-corneas-through-mmp13
#2
Nan Gao, Xiaowei Liu, Jiayin Wu, Juan Li, Chen Dong, Xinyi Wu, Xiao Xiao, Fu-Shin X Yu
Though not present in the normal adult cornea, both hem- and lymph-angiogenesis can be induced in this tissue after an inflammatory, infectious, or traumatic insult. We previously showed that the chemokine CXCL10 plays a key role in eradicating invading Candida (C.) albicans in C57BL6 mouse corneas. However, even after the clearance of pathogens, infection-induced inflammation and angiogenesis continue to progress in the cornea. The aim of this study is define the role of CXCL10 as a major angiostatic factor in modulating cornea angiogenesis in B6 mouse corneas under pathogenic conditions...
June 16, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28619088/chemokine-signals-are-crucial-for-enhanced-homing-and-differentiation-of-circulating-osteoclast-progenitor-cells
#3
Alan Sucur, Zrinka Jajic, Marinko Artukovic, Marina Ikic Matijasevic, Branimir Anic, Darja Flegar, Antonio Markotic, Tomislav Kelava, Sanja Ivcevic, Natasa Kovacic, Vedran Katavic, Danka Grcevic
BACKGROUND: The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy...
June 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28615725/transcriptome-analysis-reveals-similarities-between-human-blood-cd3-cd56-bright-cells-and-mouse-cd127-innate-lymphoid-cells
#4
David S J Allan, Ana Sofia Cerdeira, Anuisa Ranjan, Christina L Kirkham, Oscar A Aguilar, Miho Tanaka, Richard W Childs, Cynthia E Dunbar, Jack L Strominger, Hernan D Kopcow, James R Carlyle
For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3(-) CD56(bright) CD16(-) and CD3(-) CD56(dim) CD16(+) subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56(bright) cells, by gene set enrichment analysis...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615072/chemokine-receptor-co-expression-reveals-aberrantly-distributed-th-effector-memory-cells-in-gpa-patients
#5
Lucas L Lintermans, Abraham Rutgers, Coen A Stegeman, Peter Heeringa, Wayel H Abdulahad
BACKGROUND: Persistent expansion of circulating CD4(+) effector memory T cells (TEM) in patients with granulomatosis with polyangiitis (GPA) suggests their fundamental role in disease pathogenesis. Recent studies have shown that distinct functional CD4(+) TEM cell subsets can be identified based on expression patterns of chemokine receptors. The current study aimed to determine different CD4(+) TEM cell subsets based on chemokine receptor expression in peripheral blood of GPA patients...
June 14, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28599423/induction-of-cathepsin-b-by-the-cxcr3-chemokines-cxcl9-and-cxcl10-in-human-breast-cancer-cells
#6
Holger Bronger, Anne Karge, Tobias Dreyer, Daniela Zech, Sara Kraeft, Stefanie Avril, Marion Kiechle, Manfred Schmitt
Cathepsin B (CTSB) is a lysosomal cysteine protease that has been linked to the progression of breast cancer, for example by activation of other proteases and tumor-promoting cytokines, thereby supporting tumor invasion and metastasis. Previously, it was shown that CTSB cleaves and inactivates C-X-C motif chemokine receptor 3 (CXCR3) chemokines. As CXCR3 ligands have been demonstrated to induce proteases in cancer cells, the present study hypothesized that they may also affect CTSB in breast cancer cells. The results demonstrated that the human breast cancer tumor cell lines MCF-7 and MDA-MB-231 express the CXCR3 splice variants A and B and CTSB...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28569792/loss-of-epidermal-ap1-transcription-factor-function-reduces-filaggrin-level-alters-chemokine-expression-and-produces-an-ichthyosis-related-phenotype
#7
Christina A Young, Ellen A Rorke, Gautam Adhikary, Wen Xu, Richard L Eckert
AP1 transcription factors are important controllers of epidermal differentiation. Multiple family members are expressed in the epidermis in a differentiation-dependent manner, where they function to regulate gene expression. To study the role of AP1 factor signaling, TAM67 (dominant-negative c-jun) was inducibly expressed in the suprabasal epidermis. The TAM67-positive epidermis displays keratinocyte hyperproliferation, hyperkeratosis and parakeratosis, delayed differentiation, extensive subdermal vasodilation, nuclear loricrin localization, tail and digit pseudoainhum and reduced filaggrin level...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28569167/increased-serum-concentrations-of-il-1-beta-il-21-and-th17-cells-in-overweight-patients-with-rheumatoid-arthritis
#8
Hirofumi Shoda, Yasuo Nagafuchi, Yumi Tsuchida, Keiichi Sakurai, Shuji Sumitomo, Keishi Fujio, Kazuhiko Yamamoto
BACKGROUNDS: Obesity is associated with worse disease activity and drug responses in patients with rheumatoid arthritis (RA). However, the immunological mechanisms responsible for the relationship between RA and obesity have not yet been clarified in detail. This study aimed to elucidate the immunological mechanisms contributing to the pathogenesis of RA in overweight patients. METHODS: The frequencies of CD4(+) T cell, B cell and monocyte subsets were analyzed in RA (n = 81) and healthy donors (n = 99) by flow cytometry, and were compared between three groups (body mass index (BMI) <20,  ≥20 to 25, >25)...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28566856/immunophenotypic-and-molecular-analysis-of-human-dental-pulp-stem-cells-potential-for-neurogenic-differentiation
#9
Nikhat Fatima, Aleem A Khan, Sandeep K Vishwakarma
BACKGROUND: Growing evidence shows that dental pulp (DP) tissues could be a potential source of adult stem cells for the treatment of devastating neurological diseases and several other conditions. AIMS: Exploration of the expression profile of several key molecular markers to evaluate the molecular dynamics in undifferentiated and differentiated DP-derived stem cells (DPSCs) in vitro. SETTINGS AND DESIGN: The characteristics and multilineage differentiation ability of DPSCs were determined by cellular and molecular kinetics...
January 2017: Contemporary Clinical Dentistry
https://www.readbyqxmd.com/read/28564491/abatacept-attenuates-t-follicular-helper-cell-dependent-b-cell-hyperactivity-in-primary-sj%C3%A3-gren-s-syndrome
#10
Gwenny M Verstappen, Petra M Meiners, Odilia B J Corneth, Annie Visser, Suzanne Arends, Wayel H Abdulahad, Rudi W Hendriks, Arjan Vissink, Frans G M Kroese, Hendrika Bootsma
Objective To assess the effect of abatacept (CTLA-4-Ig), which limits T-cell activation, on homeostasis of CD4(+) T-cell subsets and T-cell-dependent B-cell hyperactivity in patients with primary Sjögren's syndrome (pSS). Methods Fifteen pSS patients treated with abatacept were included. Circulating CD4(+) T-cell and B-cell subsets were analyzed by flow cytometry at baseline, on treatment and off treatment. CD4(+) effector T-cell subsets and T regulatory (Treg)-cells were identified based on expression of CD45RA, CXCR3, CCR6, CCR4, CXCR5, programmed death-1 (PD-1), inducible costimulator (ICOS) and FoxP3...
May 31, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28559424/c-x-c-motif-chemokine-receptor-3-splice-variants-differentially-activate-beta-arrestins-to-regulate-downstream-signaling-pathways
#11
Jeffrey S Smith, Priya Alagesan, Nimit K Desai, Thomas F Pack, Jiao-Hui Wu, Asuka Inoue, Neil J Freedman, Sudarshan Rajagopal
Biased agonism, the ability of different ligands for the same receptor to selectively activate some signaling pathways while blocking others, is now an established paradigm for GPCR signaling. One group of receptors in which endogenous bias is critical is the chemokine system, consisting of over 50 ligands and 20 receptors that bind one another with significant promiscuity. We have previously demonstrated that ligands for the same receptor can cause biased signaling responses. The goal of this study was to identify mechanisms that could underlie biased signaling between different receptor splice variants...
May 30, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28554560/th1-phenotype-of-t-follicular-helper-cells-indicates-an-ifn%C3%AE-associated-immune-dysregulation-in-cd21low-cvid-patients
#12
Susanne Unger, Maximilian Seidl, Pauline van Schouwenburg, Mirzokhid Rakhmanov, Alla Bulashevska, Natalie Frede, Bodo Grimbacher, Jens Pfeiffer, Klaudia Schrenk, Luis Munoz, Leif Hanitsch, Ina Stumpf, Fabian Kaiser, Oliver Hausmann, Florian Kollert, Sigune Goldacker, Mirjam van der Burg, Baerbel Keller, Klaus Warnatz
BACKGROUND: A subgroup of patients with Common Variable Immunodeficiency (CVID) suffers from immune dysregulation, manifesting as autoimmunity, lymphoproliferation and organ inflammation, and thereby increasing morbidity and mortality. Therefore, treatment of these complications demands a deeper comprehension of their etiology and pathophysiology. OBJECTIVES: Based on the identification of an Interferon (IFN) signature in CVID patients with secondary complications and a skewed T follicular helper cell (TFH) differentiation in defined monogenic immunodeficiencies, we sought to determine the profile of CD4 memory T cells in blood and secondary lymphatic tissues of these patients...
May 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#13
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#14
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#15
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526557/the-frog-skin-host-defense-peptide-frenatin-2-1s-enhances-recruitment-activation-and-tumoricidal-capacity-of-nk-cells
#16
Jelena M Pantic, Ivan P Jovanovic, Gordana D Radosavljevic, Nevena M Gajovic, Nebojsa N Arsenijevic, J Michael Conlon, Miodrag L Lukic
Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity...
May 16, 2017: Peptides
https://www.readbyqxmd.com/read/28518224/t-helper-1-related-molecules-as-well-as-il-15-are-hyperexpressed-in-the-skin-lesions-of-patients-with-pyoderma-gangrenosum
#17
Emiliano Antiga, Roberto Maglie, Walter Volpi, Beatrice Bianchi, Emilio Berti, Angelo Valerio Marzano, Marzia Caproni
Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Whether a number of studies confirmed the central role of innate immunity, only few studies investigated the possible contributing role of acquired immunity. In particular, no reports about Th1 and Th2 cells are available yet. Therefore, 15 patients with PG, 5 with Sweet's syndrome (SS) and 9 skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers IL-12, IFN-γ, CXCR3, CCR5, of the Th2 related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40L, of IL-15 and the NK cell marker CD56 in skin lesions by immunohistochemistry...
May 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28516880/abatacept-therapy-reduces-cd28-cxcr5-follicular-helper-like-t-cells-in-patients-with-rheumatoid-arthritis
#18
Shunsuke Fukuyo, Shingo Nakayamada, Shigeru Iwata, Satoshi Kubo, Kazuyoshi Saito, Yoshiya Tanaka
OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT. METHODS: We analysed the peripheral T cell phenotype of 34 RA patients via flow cytometry. The correlation of the phenotypes of CD4+ T cells with clinical disease activity and change in CD4+ T cell subsets at baseline and 24 weeks after ABT treatment were evaluated...
April 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28504691/cxcr3-mediates-ascites-directed-tumor-cell-migration-and-predicts-poor-outcome-in-ovarian-cancer-patients
#19
C Windmüller, D Zech, S Avril, M Boxberg, T Dawidek, B Schmalfeldt, M Schmitt, M Kiechle, H Bronger
Intraabdominal tumor dissemination is a major hallmark of epithelial ovarian cancer (EOC), but the underlying mechanisms have not been fully elucidated. The CXCR3 chemokine receptor supports migration of tumor cells to metastatic sites, but its role in ovarian cancer metastasis is largely unknown. Herein, we first screened two independent cohorts of high-grade serous ovarian cancers (HGSCs, discovery set n=60, validation set n=117) and 102 metastatic lesions for CXCR3 expression. In primary tumors, CXCR3 was particularly overexpressed by tumor cells at the invasive front...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28500070/cxcr3-1-and-cxcr3-2-differentially-contribute-to-macrophage-polarization-in-teleost-fish
#20
Xin-Jiang Lu, Qiang Chen, Ye-Jing Rong, Feng Chen, Jiong Chen
The study of multiple copies of chemokine receptor genes in various teleosts has long appealed to investigators seeking to understand the evolution of the immune system. The CXCR CXCR3 gene has two isoforms, CXCR3.1 and CXCR3.2, which are both expressed in macrophages. The distinct roles of teleost CXCR3s have not been identified previously. In this article, we found that CXCR3.1 and CXCR3.2 differentially contributed to macrophage polarization in the teleosts: ayu (Plecoglossus altivelis), grass carp (Ctenopharyngodon idella), and spotted green pufferfish (Tetraodon nigroviridis)...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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