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https://www.readbyqxmd.com/read/28745326/defective-positioning-in-granulomas-but-not-lung-homing-limits-cd4-t-cell-interactions-with-mycobacterium-tuberculosis-infected-macrophages-in-rhesus-macaques
#1
K D Kauffman, M A Sallin, S Sakai, O Kamenyeva, J Kabat, D Weiner, M Sutphin, D Schimel, L Via, C E Barry, T Wilder-Kofie, I Moore, R Moore, D L Barber
Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3(+) CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1(+) terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28744018/cxcl10-is-produced-in-hepatitis-a-virus-infected-cells-in-an-irf3-dependent-but-ifn-independent-manner
#2
Pil Soo Sung, Seon-Hui Hong, Jeewon Lee, Su-Hyung Park, Seung Kew Yoon, Woo Jin Chung, Eui-Cheol Shin
Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by severe liver injury in adult patients, and the liver injury is associated with the production of chemokines. Herein, we investigated the mechanism of how HAV infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10, CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2 cells. In particular, CXCL10 was produced in HAV-infected cells, not in neighboring uninfected cells...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28742087/type-1-skewed-neuroinflammation-and-vascular-damage-associated-with-orientia-tsutsugamushi-infection-in-mice
#3
Lynn Soong, HeThomas R Shelite, Yan Xing, Harica Kodakandla, Yuejin Liang, Brandon J Trent, Paulina Horton, Kathryn C Smith, Zhenyang Zhao, Jiaren Sun, Donald H Bouyer, Jiyang Cai
BACKGROUND: Scrub typhus is a life-threatening disease, due to infection with O. tsutsugamushi, a Gram-negative bacterium that preferentially replicates in endothelial cells and professional phagocytes. Meningoencephalitis has been reported in scrub typhus patients and experimentally-infected animals; however, the neurological manifestation and its underlying mechanisms remain poorly understood. To address this issue, we focused on Orientia tsutsugamushi Karp strain (OtK), and examined host responses in the brain during lethal versus self-healing scrub typhus disease in our newly established murine models...
July 24, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28724396/pathogenic-roles-of-cxcl10-signaling-through-cxcr3-and-tlr4-in-macrophages-and-t-cells-relevance-for-arthritis
#4
Jong-Ho Lee, Bongjun Kim, Won Jong Jin, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by uncontrolled joint inflammation and destruction of bone and cartilage. We previously reported that C-X-C motif chemokine 10 (CXCL10; also called IP-10) has important roles in joint inflammation and bone destruction in arthritis. However, the specific mechanisms by which CXCL10 regulates the recruitment of inflammatory cells and the production of osteoclastogenic cytokines in RA progression are not fully understood...
July 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28710773/reciprocal-modulation-of-helper-th1-and-th17-cells-by-the-%C3%AE-2-adrenergic-receptor-agonist-drug-terbutaline
#5
Catalina M Carvajal Gonczi, Mahdieh Tabatabaei Shafiei, Ashley East, Erika Martire, Meagane H I Maurice-Ventouris, Peter J Darlington
Catecholamine hormones are powerful regulators of the immune system produced by the sympathetic nervous system. They regulate the adaptive immune system by altering T cell differentiation into T helper (Th) 1 and Th2 cell subsets, but the effect on Th17 cells is not known. Th17 cells, defined in part by chemokine receptor CCR6 and cytokine IL-17A, are crucial for mediating certain pathogen-specific responses, and are linked with several autoimmune diseases. We demonstrated that a proportion of human Th17 cells express β2-adrenergic receptor, a G protein coupled receptor that responds to catecholamines...
July 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28710387/protein-tyrosine-phosphatase-inhibition-prevents-experimental-cerebral-malaria-by-precluding-cxcr3-expression-on-t-cells
#6
Kristin M Van Den Ham, Logan K Smith, Martin J Richer, Martin Olivier
Cerebral malaria induced by Plasmodium berghei ANKA infection is dependent on the sequestration of cytotoxic T cells within the brain and augmentation of the inflammatory response. Herein, we demonstrate that inhibition of protein tyrosine phosphatase (PTP) activity significantly attenuates T cell sequestration within the brain and prevents the development of neuropathology. Mechanistically, the initial upregulation of CXCR3 on splenic T cells upon T cell receptor stimulation was critically decreased through the reduction of T cell-intrinsic PTP activity...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705088/a-study-of-comparative-modelling-simulation-and-molecular-dynamics-of-cxcr3-receptor-with-lipid-bilayer
#7
Dhivya Shanmugarajan, C Suresh Kumar, Vijayakumar Bommuraj, Rethavathi Janarthanam, Meena Chandran, Usha Talambedu, Sushilkumar Middha
The G-coupled receptors seen on the cell surface are composites with a lipid bilayer. The chemokines are kind of G-coupled receptor which majorly involved in the activation and downstream signalling of the cell. In general, many G-coupled receptors are lack of its 3D structure that become a hurdle in the drug designing process. In this study, comparative modelling of the CXCR3 receptor was carried out, structure evaluation was done using various tools and software's. Additionally, molecular dynamics and docking were performed to prove the structural quality and architecture...
July 14, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28701512/imatinib-and-nilotinib-off-target-effects-on-human-nk-cells-monocytes-and-m2-macrophages
#8
Francesca Bellora, Alessandra Dondero, Maria Valeria Corrias, Beatrice Casu, Stefano Regis, Fabio Caliendo, Alessandro Moretta, Mario Cazzola, Chiara Elena, Luciana Vinti, Franco Locatelli, Cristina Bottino, Roberta Castriconi
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701399/selective-expression-of-ccr10-and-cxcr3-by-circulating-human-hsv-specific-cd8-t-cells
#9
Michael T Hensel, Tao Peng, Anqi Cheng, Stephen C De Rosa, Anna Wald, Kerry J Laing, Lichen Jing, Lichun Dong, Amalia S Magaret, David M Koelle
Herpes simplex virus type (HSV) infection is restricted to epithelial cells and neurons and is controlled by CD8 T-cells. These cells both traffic to epithelial sites of recurrent lytic infection and to ganglia, and persist at the dermal-epidermal junction for up to 12 weeks after lesion resolution. We previously showed that cutaneous lymphocyte-associated antigen (CLA), a functional E-selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8 T-cells. CLA/ESL mediates adhesion of T-cells to inflamed vascular endothelium...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28686641/the-prognostic-importance-of-cxcr3-chemokine-during-organizing-pneumonia-on-the-risk-of-chronic-lung-allograft-dysfunction-after-lung-transplantation
#10
Michael Y Shino, S Samuel Weigt, Ning Li, Vyacheslav Palchevskiy, Ariss Derhovanessian, Rajan Saggar, David M Sayah, Richard H Huynh, Aric L Gregson, Michael C Fishbein, Abbas Ardehali, David J Ross, Joseph P Lynch, Robert M Elashoff, John A Belperio
RATIONALE: Since the pathogenesis of chronic lung allograft dysfunction (CLAD) remains poorly defined with no known effective therapies, the identification and study of key events which increase CLAD risk is a critical step towards improving outcomes. We hypothesized that bronchoalveolar lavage fluid (BALF) CXCR3 ligand concentrations would be augmented during organizing pneumonia (OP) and that episodes of OP with marked chemokine elevations would be associated with significantly higher CLAD risk...
2017: PloS One
https://www.readbyqxmd.com/read/28679952/severe-asthma-in-humans-and-mouse-model-suggests-a-cxcl10-signature-underlies-corticosteroid-resistant-th1-bias
#11
Marc Gauthier, Krishnendu Chakraborty, Timothy B Oriss, Mahesh Raundhal, Sudipta Das, Jie Chen, Rachael Huff, Ayan Sinha, Merritt Fajt, Prabir Ray, Sally E Wenzel, Anuradha Ray
We previously showed that Th1/type 1 inflammation marked by increased IFN-γ levels in the airways can be appreciated in 50% of patients with severe asthma, despite high dose corticosteroid (CS) treatment. We hypothesized that a downstream target of IFN-γ, CXCL10, which recruits Th1 cells via the cognate receptor CXCR3, is an important contributor to Th1high asthma and CS unresponsiveness. We show high levels of CXCL10 mRNA closely associated with IFNG levels in the BAL cells of 50% of severe asthmatics and also in the airways of mice subjected to a severe asthma model, both in the context of high-dose CS treatment...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28674001/delineation-of-an-immunosuppressive-gradient-in-hepatocellular-carcinoma-using-high-dimensional-proteomic-and-transcriptomic-analyses
#12
Valerie Chew, Liyun Lai, Lu Pan, Chun Jye Lim, Juntao Li, Raymond Ong, Camillus Chua, Jing Yao Leong, Kiat Hon Lim, Han Chong Toh, Ser Yee Lee, Chung Yip Chan, Brian K P Goh, Alexander Chung, Pierce K H Chow, Salvatore Albani
The recent development of immunotherapy as a cancer treatment has proved effective over recent years, but the precise dynamics between the tumor microenvironment (TME), nontumor microenvironment (NTME), and the systemic immune system remain elusive. Here, we interrogated these compartments in hepatocellular carcinoma (HCC) using high-dimensional proteomic and transcriptomic analyses. By time-of-flight mass cytometry, we found that the TME was enriched in regulatory T cells (Tregs), tissue resident memory CD8(+) T cells (TRMs), resident natural killer cells (NKRs), and tumor-associated macrophages (TAMs)...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28667746/integrated-gut-liver-microphysiological-systems-elucidates-inflammatory-inter-tissue-crosstalk
#13
Wen L K Chen, Collin Edington, Emily Suter, Jiajie Yu, Jeremy J Velazquez, Jason G Velazquez, Michael Shockley, Emma M Large, Raman Venkataramanan, David J Hughes, Cynthia L Stokes, David L Trumper, Rebecca L Carrier, Murat Cirit, Linda G Griffith, Douglas A Lauffenburger
A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut-liver tissue interactions under normal and inflammatory contexts, via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models...
July 1, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28652655/effect-of-cxcr3-ho-1-genes-modified-bone-marrow-mesenchymal-stem-cells-on-small-bowel-transplant-rejection
#14
Ming-Li Yin, Hong-Li Song, Yang Yang, Wei-Ping Zheng, Tao Liu, Zhong-Yang Shen
AIM: To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection. METHODS: Lewis rat BMMSCs were cultured in vitro. Third-passage BMMSCs were transduced with the CXCR3/HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to small bowel transplant...
June 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28651949/%C3%AE-%C3%AE-t-cell-function-is-inhibited-in-end-stage-renal%C3%A2-disease-and-impacted-by-latent-tuberculosis%C3%A2-infection
#15
Jennifer A Juno, Jillian L M Waruk, Angela Harris, Christine Mesa, Carmen Lopez, Joe Bueti, T Blake Ball, Sandra A Kiazyk
Patients with end-stage renal disease (ESRD) are at elevated risk of acquiring infectious diseases, including tuberculosis (TB). Inflammation and uremia negatively impact immune function in this population, but specific pathways involved in TB immunity have not been identified. Although γδ T cells are known to contribute to protection from TB, their phenotype and function in patients with ESRD is relatively unknown. To determine this we recruited 20 patients with and 20 without ESRD (controls), with or without latent TB infection to assess γδ T cell frequency, surface phenotype, and cytokine production by flow cytometry in response to stimulation...
June 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28650992/galectin-8-as-an-immunosuppressor-in-experimental-autoimmune-encephalomyelitis-and-a-target-of-human-early-prognostic-antibodies-in-multiple-sclerosis
#16
Evelyn Pardo, Claudia Cárcamo, Reinaldo Uribe-San Martín, Ethel Ciampi, Fabián Segovia-Miranda, Cristobal Curkovic-Peña, Fabián Montecino, Christopher Holmes, Juan Enrique Tichauer, Eric Acuña, Francisco Osorio-Barrios, Marjorie Castro, Priscilla Cortes, Claudia Oyanadel, David M Valenzuela, Rodrigo Pacheco, Rodrigo Naves, Andrea Soza, Alfonso González
Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients...
2017: PloS One
https://www.readbyqxmd.com/read/28638727/identification-of-an-immunogenic-neo-epitope-encoded-by-mouse-sarcoma-using-cxcr3-ligand-mrnas-as-sensors
#17
Keisuke Fujii, Yoshihiro Miyahara, Naozumi Harada, Daisuke Muraoka, Mitsuhiro Komura, Rui Yamaguchi, Hideo Yagita, Junko Nakamura, Sahoko Sugino, Satoshi Okumura, Seiya Imoto, Satoru Miyano, Hiroshi Shiku
The CXCR3 ligands CXCL9, 10, and 11 play critical roles in the amplification of immune responses by recruiting CXCR3(+) immune effector cells to the tumor site. Taking advantage of this property of CXCR3 ligands, we aimed to establish a novel approach to identify immunogenic mutated-antigens. We examined the feasibility of using CXCR3 ligand mRNAs as sensors for detection of specific immune responses in human and murine systems. We further investigated whether this approach is applicable for the identification of immunogenic mutated-antigens by using murine sarcoma lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637878/cd4-t-cell-and-nk-cell-interplay-key-to-regression-of-mhc-class-i-low-tumors-upon-tlr7-8-agonist-therapy
#18
Elien M Doorduijn, Marjolein Sluijter, Daniela C Salvatori, Serenella Silvestri, Saskia Maas, Ramon Arens, Ferry Ossendorp, Sjoerd H van der Burg, Thorbald van Hall
One of the next challenges in cancer immunotherapy is the resistance of tumors to T cell-based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4(+) T cells, whereas activated CD8(+) T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice...
June 21, 2017: Cancer Immunology Research
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
#19
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...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28623423/cxcl10-suppression-of-hem-and-lymph-angiogenesis-in-inflamed-corneas-through-mmp13
#20
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
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