Infiltration Into Antigen-Challenged Skin Perforin Directs Effector CD8 T
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Complementary DNA Microarray Analysis of Chemokines and Their Receptors in Allergic Rhinitis RX Zhang,1 SQ Yu,2 JZ Jiang,3 GJ Liu3
RX Zhang, et al ORIGINAL ARTICLE Complementary DNA Microarray Analysis of Chemokines and Their Receptors in Allergic Rhinitis RX Zhang,1 SQ Yu,2 JZ Jiang,3 GJ Liu3 1 Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, China 2 Department of Otolaryngology , Jinan General Hospital of PLA, Shandong, China 3 Department of Otolaryngology, Changhai Hospital, Second Military Medical University, Shanghai, China ■ Abstract Objective: To analyze the roles of chemokines and their receptors in the pathogenesis of allergic rhinitis by observing the complementary DNA (cDNA) expression of the chemokines and their receptors in the nasal mucosa of patients with and without allergic rhinitis, using gene chips. Methods: The total RNAs were isolated from the nasal mucosa of 20 allergic rhinitis patients and purifi ed to messenger RNAs, and then reversely transcribed to cDNAs and incorporated with samples of fl uorescence-labeled with Cy5-dUPT (rhinitis patient samples) or Cy3- dUTP (control samples of nonallergic nasal mucosa). Thirty-nine cDNAs of chemokines and their receptors were latticed into expression profi le chips, which were hybridized with probes and then scanned with the computer to study gene expression according to the different fl uorescence intensities. Results: The cDNAs of the following chemokines were upregulated: CCL1, CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL14, CCL17, CCL18, CCL19, CCL24, and CX3CL1 in most of the allergic rhinitis sample chips. CCR2, CCR3, CCR4, CCR5, CCR8 and CX3CR1 were the highly expressed receptor genes. Low expression of CXCL4 was found in these tissues. Conclusion: The T helper cell (TH) immune system is not well regulated in allergic rhinitis. -
Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance As a Prognostic Biomarker in Ovarian
cells Review Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients Michal Kielbik *, Izabela Szulc-Kielbik and Magdalena Klink Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa Str., 93-232 Lodz, Poland; [email protected] (I.S.-K.); [email protected] (M.K.) * Correspondence: [email protected]; Tel.: +48-42-27-23-636 Abstract: Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases. Chemotherapeutics, radiotherapy and photodynamic therapy induce intracellular stress response pathways in tumor cells, leading to a secretion of various factors belonging to a family of damage-associated molecular patterns molecules, capable of inducing the adaptive immune response. One of them is calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on the surface of dying tumor cells serves as an “eat me” signal for antigen presenting cells (APC). Engulfment of tumor cells by APCs results in the presentation of tumor’s antigens to cytotoxic T-cells and production of cytokines/chemokines, which activate immune cells responsible for tumor cells killing. Thus, the development of ICD and the expression of CRT can help standard therapy to eradicate tumor cells. Here, we review the physiological functions of CRT and its involvement in the ICD appearance in malignant dis- ease. Moreover, we also focus on the ability of various anti-cancer drugs to induce expression of surface CRT on ovarian cancer cells. The second aim of this work is to discuss and summarize the prognostic/predictive value of CRT in ovarian cancer patients. -
Bioinformatics Identification of CCL8/21 As Potential Prognostic
Bioscience Reports (2020) 40 BSR20202042 https://doi.org/10.1042/BSR20202042 Research Article Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment 1,* 2,* 3 4 5 1 Bowen Chen , Shuyuan Zhang ,QiuyuLi, Shiting Wu ,HanHe and Jinbo Huang Downloaded from http://portlandpress.com/bioscirep/article-pdf/40/11/BSR20202042/897847/bsr-2020-2042.pdf by guest on 28 September 2021 1Department of Breast Disease, Maoming People’s Hospital, Maoming 525000, China; 2Department of Clinical Laboratory, Maoming People’s Hospital, Maoming 525000, China; 3Department of Emergency, Maoming People’s Hospital, Maoming 525000, China; 4Department of Oncology, Maoming People’s Hospital, Maoming 525000, China; 5Department of Medical Imaging, Maoming People’s Hospital, Maoming 525000, China Correspondence: Shuyuan Zhang ([email protected]) Background: Breast cancer (BC) is the most common malignancy among females world- wide. The tumor microenvironment usually prevents effective lymphocyte activation and infiltration, and suppresses infiltrating effector cells, leading to a failure of the host toreject the tumor. CC chemokines play a significant role in inflammation and infection. Methods: In our study, we analyzed the expression and survival data of CC chemokines in patients with BC using several bioinformatics analyses tools. Results: The mRNA expression of CCL2/3/4/5/7/8/11/17/19/20/22 was remark- ably increased while CCL14/21/23/28 was significantly down-regulated in BC tis- sues compared with normal tissues. Methylation could down-regulate expression of CCL2/5/15/17/19/20/22/23/24/25/26/27 in BC. Low expression of CCL3/4/23 was found to be associated with drug resistance in BC. -
Induced CNS Expression of CXCL1 Augments Neurologic Disease in a Murine Model of Multiple Sclerosis Via Enhanced Neutrophil Recruitment
Eur. J. Immunol. 2018. 48: 1199–1210 DOI: 10.1002/eji.201747442 Jonathan J. Grist et al. 1199 Basic Immunodeficiencies and autoimmunity Research Article Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment Jonathan J. Grist1, Brett S. Marro3, Dominic D. Skinner1, Amber R. Syage1, Colleen Worne1, Daniel J. Doty1, Robert S. Fujinami1,2 andThomasE.Lane1,2 1 Department of Pathology, Division of Microbiology and Immunology, University of Utah, School of Medicine, Salt Lake City, UT, USA 2 Immunology, Inflammation, and Infectious Disease Initiative, University of Utah, UT, USA 3 Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. There- fore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular com- ponents that contribute to disease in MS patients. In this study, we examined the func- tional role of the chemokine CXCL1 in contributing to neuroinflammation and demyeli- nation in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b+Ly6G+ neutrophils into the spinal cord. -
Apoptosis by Incomplete Infection
rESEArcH HIGHLIGHtS Apoptosis by incomplete infection Constraining inflammation κ Infection with human immunodeficiency virus (HIV) is The transcription factor NF- B is a critical mediator of Toll-like recep- characterized by progressive apoptosis of CD4+ T cells, and tor (TLR) signaling in response to a range of activators. In Genes & although some of the molecular participants in this process are Development, Barish et al. provide genetic and genomic evidence that known, the precise details remain unclear. Greene and colleagues the transcription factor Bcl-6 broadly antagonizes the TLR–NF-κB in Cell report the unexpected finding that nonproductive infection network. Genome-wide expression analyses and chromatin-immuno- of CD4+ T cells can also result in apoptosis. The authors use a precipitation sequencing (ChIP-Seq) show that Bcl-6 is a basal- and human lymphoid aggregation culture system to recapitulate in lipopolysaccharide (LPS)-induced inhibitor of many inflammatory vitro the events of HIV infection in the lymph node. The addition modules in bone marrow–derived macrophages. Bcl-6 controls one of HIV to this culture system results in the apoptosis of not only third of the LPS-elicited transcriptome, and sites for Bcl-6 and the productively infected but also nonpermissive CD4+ cells. Apoptosis NF-κB subunit p65 are located together in a nucleosomal window of the latter requires fusion with HIV and the initiation but not (200 base pairs) in 25% of the gene network controlled by TLR–NF-κB. completion of viral reverse transcription. The accumulation Stimulation of TLR4 reciprocally diminishes or enhances the binding of of incomplete HIV reverse transcripts results in activation of Bcl-6 and p65 to enhancer regions at target genes encoding key inflam- caspase-1 and caspase-3 and release of the inflammatory cytokine matory molecules, such as IL-1 and various chemokines. -
The Chemokine System in Innate Immunity
Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press The Chemokine System in Innate Immunity Caroline L. Sokol and Andrew D. Luster Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114 Correspondence: [email protected] Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system. Chemokines control the release of innate immune cells from the bone marrow during homeostasis as well as in response to infection and inflammation. Theyalso recruit innate immune effectors out of the circulation and into the tissue where, in collaboration with other chemoattractants, they guide these cells to the very sites of tissue injury. Chemokine function is also critical for the positioning of innate immune sentinels in peripheral tissue and then, following innate immune activation, guiding these activated cells to the draining lymph node to initiate and imprint an adaptive immune response. In this review, we will highlight recent advances in understanding how chemokine function regulates the movement and positioning of innate immune cells at homeostasis and in response to acute inflammation, and then we will review how chemokine-mediated innate immune cell trafficking plays an essential role in linking the innate and adaptive immune responses. hemokines are chemotactic cytokines that with emphasis placed on its role in the innate Ccontrol cell migration and cell positioning immune system. throughout development, homeostasis, and in- flammation. The immune system, which is de- pendent on the coordinated migration of cells, CHEMOKINES AND CHEMOKINE RECEPTORS is particularly dependent on chemokines for its function. -
Critical Role of CXCL4 in the Lung Pathogenesis of Influenza (H1N1) Respiratory Infection
ARTICLES Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection L Guo1,3, K Feng1,3, YC Wang1,3, JJ Mei1,2, RT Ning1, HW Zheng1, JJ Wang1, GS Worthen2, X Wang1, J Song1,QHLi1 and LD Liu1 Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection. Additionally, CXCL4 deficiency decreased leukocyte accumulation in the infected lung with markedly decreased neutrophil infiltration into the lung during early infection and extensive leukocyte, especially lymphocyte accumulation at the late infection stage. Loss of CXCL4 did not affect the activation of adaptive immune T and B lymphocytes during the late stage of lung infection. Further study revealed that CXCL4 deficiency inhibited neutrophil recruitment to the infected mouse lung. Thus the above results identify CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung. INTRODUCTION necrosis factor (TNF)-a, interleukin (IL)-6, and IL-1b, to exert Influenza A virus (IAV) infections cause respiratory diseases in further antiviral innate immune effects.2 Meanwhile, the innate large populations worldwide every year and result in seasonal immune cells act as antigen-presenting cells and release influenza epidemics and unexpected pandemic. -
Metastasis: Active Lymph Nodes
RESEARCH HIGHLIGHTS METASTASIS subcapsular sinus. Further investiga- tions in vivo revealed that CCR8 acti- vation in tumour cells was required Active lymph nodes for tumour cell extravasation from lymphatic vessels, specifically for the Lymph node metastases are CCL1 activates CCR8-mediated transmigration of tumour cells from indicative of poor prognosis but intracellular signalling in tumour the subcapsular sinus into the lymph tumour cell the mechanisms of tumour cell cells, which resulted in cellular node cortex. entry into the dissemination via the lymphatics changes that are consistent with cell These data unpick the process of are poorly understood. Although it migration. lymphatic dissemination and iden- lymph node is widely believed that tumour cells Is the CCR8–CCL1 paracrine tify the sequence of steps leading to requires active enter the lymph nodes passively with pathway important in lymphatic lymph node metastasis. The authors cell migration the flow of lymph, previous data have metastasis? The suppression of showed that CCR8 is expressed by indicated that some chemokines may CCR8 expression or activity in a large subset of human melanoma promote lymphatic extravasation human melanoma cells did not samples, and it will be interesting and metastasis. Das et al. now dem- affect tumour growth or vasculariz to determine whether this pathway onstrate that tumour cell entry into ation on implantation into immuno can be targeted to prevent lymph the lymph node requires active cell deficient mice, but significantly node metastasis. migration and they also identify the reduced the incidence of lymph Gemma K. Alderton lymphatic endothelium of the lymph node metastasis. Furthermore, ORIGINAL RESEARCH PAPER Das, S. -
Exploration of Prognostic Biomarkers and Therapeutic Targets in the Microenvironment of Bladder Cancer Based on CXC Chemokines
Exploration of Prognostic Biomarkers and Therapeutic Targets in The Microenvironment of Bladder Cancer Based on CXC Chemokines Xiaoqi Sun Department of Urology, Kaiping Central Hospital, Kaiping, 529300, China Qunxi Chen Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China Lihong Zhang Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China Jiewei Chen Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China Xinke Zhang ( [email protected] ) Sun Yat-sen University Cancer Center Research Keywords: Bladder cancer, Biomarkers, CXC Chemokines, Microenvironment Posted Date: February 24th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-223127/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/29 Abstract Background: Bladder cancer (BLCA) has a high rate of morbidity and mortality, and is considered as one of the most malignant tumors of the urinary system. Tumor cells interact with surrounding interstitial cells, playing a key role in carcinogenesis and progression, which is partly mediated by chemokines. CXC chemokines exert anti‐tumor biological roles in the tumor microenvironment and affect patient prognosis. Nevertheless, their expression and prognostic values patients with BLCA remain unclear. Methods: We used online tools, including Oncomine, UALCAN, GEPIA, GEO databases, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRUST (version 2.0), LinkedOmics, TCGA, and TIMER2.0 to perform the relevant analysis. Results: The mRNA levels of C-X-C motif chemokine ligand (CXCL)1, CXCL5, CXCL6, CXCL7, CXCL9, CXCL10, CXCL11, CXCL13, CXCL16, and CXCL17 were increased signicantly increased, and those of CXCL2, CXCL3, and CXCL12 were decreased signicantly in BLCA tissues as assessed using the Oncomine, TCGA, and GEO databases. -
Identification of CCL1 As a Gene Differentially Expressed in CD4+ T Cells Expressing TIM-3
http://dx.doi.org/10.4110/in.2011.11.4.203 ORIGINAL ARTICLE pISSN 1598-2629 eISSN 2092-6685 Identification of CCL1 as a Gene Differentially Expressed in CD4+ T cells Expressing TIM-3 Ka Jung Jun1,2, Mi Jin Lee1,2, Dong Chul Shin1,2, Min Yeong Woo1,2, Kyongmin Kim1 and Sun Park1* 1Department of Microbiology and 2Graduate Program of Molecular Medicine, Ajou University School of Medicine, Suwon 442-749, Korea Background: T cell immunoglobulin mucin containing mole- responses and the pathogenesis of several diseases (1). With cule (TIM)-3 is expressed in differentiated Th1 cells and is in- its blocking antibody or its soluble fusion protein TIM-3-Ig, volved in the suppression of the cytokine production by these Th1 immune response as well as anti-tumor immunity is en- cells. However, the regulation of the expression of other T hanced (2-4). Also, induction of tolerance in an experimental cell genes by TIM-3 is unclear. Herein, we attempted to iden- transplantation model is abrogated by injection of TIM-3 anti- tify differentially expressed genes in cells abundantly ex- body (5). Furthermore, dysregulation of T cell TIM-3 ex- pressing TIM-3 compared to cells with low expression of pression is observed in several autoimmune diseases includ- TIM-3. Methods: TIM-3 overexpressing cell clones were es- ing multiple sclerosis, rheumatoid arthritis and Crohn s dis- tablished by transfection of Jurkat T cells with TIM-3 ex- ’ pression vector. For screening of differentially expressed ease (6-8). genes, gene fishing technology based on reverse tran- Galectin-9 and phosphatidylserine have been identified as scription-polymerase chain reaction (RT-PCR) using an an- TIM-3 ligands. -
Identification of Markers Predictive for Response to Induction
Oral Oncology 97 (2019) 56–61 Contents lists available at ScienceDirect Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology Identification of markers predictive for response to induction chemotherapy in patients with sinonasal undifferentiated carcinoma T ⁎ Yoko Takahashia, ,1, Frederico O. Gleber-Nettoa,1, Diana Bellb, Dianna Robertsa, Tong-Xin Xiea, Ahmed S. Abdelmeguida,2, Curtis Pickeringa,Jeffrey N. Myersa, Ehab Y. Hannaa a Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA b Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA ARTICLE INFO ABSTRACT Keywords: Objectives: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. Despite aggressive Sinonasal undifferentiated carcinoma multimodal therapy, its prognosis remains poor. Because of its locally advanced nature and high propensity for Comprehensive gene expression study distant metastasis, we frequently use induction chemotherapy before definitive therapy in patients with SNUC. Induction chemotherapy However, about 30% of patients do not respond to induction chemotherapy, and lack of response is associated Predictive markers with a poor survival rate. Therefore, in this study, we performed gene expression analysis of SNUC samples to Chemoresistance identify prognostic markers for induction chemotherapy response. Materials and methods: Formalin-fixed, paraffin-embedded SNUC tumor samples from previously untreated pa- tients harvested before induction chemotherapy were used. Gene expression was performed using an oncology gene expression panel. Results: We identified 34 differentially expressed genes that distinguish the responders from the non-responders. Pathway analysis using these genes revealed alteration of multiple pathways between the two groups. Of these 34 genes, 24 distinguished between these two groups. -
Inflammatory Modulation of Hematopoietic Stem Cells by Magnetic Resonance Imaging
Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2014 Inflammatory modulation of hematopoietic stem cells by Magnetic Resonance Imaging (MRI)-detectable nanoparticles Sezin Aday1,2*, Jose Paiva1,2*, Susana Sousa2, Renata S.M. Gomes3, Susana Pedreiro4, Po-Wah So5, Carolyn Ann Carr6, Lowri Cochlin7, Ana Catarina Gomes2, Artur Paiva4, Lino Ferreira1,2 1CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal, 2Biocant, Biotechnology Innovation Center, Cantanhede, Portugal, 3King’s BHF Centre of Excellence, Cardiovascular Proteomics, King’s College London, London, UK, 4Centro de Histocompatibilidade do Centro, Coimbra, Portugal, 5Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK, 6Cardiac Metabolism Research Group, Department of Physiology, Anatomy & Genetics, University of Oxford, UK, 7PulseTeq Limited, Chobham, Surrey, UK. *These authors contributed equally to this work. #Correspondence to Lino Ferreira ([email protected]). Experimental Section Preparation and characterization of NP210-PFCE. PLGA (Resomers 502 H; 50:50 lactic acid: glycolic acid) (Boehringer Ingelheim) was covalently conjugated to fluoresceinamine (Sigma- Aldrich) according to a protocol reported elsewhere1. NPs were prepared by dissolving PLGA (100 mg) in a solution of propylene carbonate (5 mL, Sigma). PLGA solution was mixed with perfluoro- 15-crown-5-ether (PFCE) (178 mg) (Fluorochem, UK) dissolved in trifluoroethanol (1 mL, Sigma). This solution was then added to a PVA solution (10 mL, 1% w/v in water) dropwise and stirred for 3 h. The NPs were then transferred to a dialysis membrane and dialysed (MWCO of 50 kDa, Spectrum Labs) against distilled water before freeze-drying. Then, NPs were coated with protamine sulfate (PS).