Cytokine Regulation of Expression of Class I MHC Antigens
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Correlation of Cytokine Level with the Severity of Severe Fever With
Liu et al. Virology Journal (2017) 14:6 DOI 10.1186/s12985-016-0677-1 RESEARCH Open Access Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome Miao-Miao Liu1, Xiao-Ying Lei1, Hao Yu2, Jian-zhi Zhang3 and Xue-jie Yu1,4* Abstract Background: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. Methods: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay. Results: The results showed that IFN-α, tumor necrosis factor (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), macrophage inflammatory protein (MIP-1α), interleukin-6 (IL-6), IL-10, interferon-inducible protein (IP-10), monocyte chemoattractant protein (MCP-1) were significantly higher in SFTS patients than in healthy persons (p < 0.05); the concentrations of IFN-α, IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10 were significant higher in severe SFTS patients than in mild SFTS patients (p < 0.05). Conclusion: The concentration of IFN-α as well as other cytokines (IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10) is correlated with the severity of SFTS, suggesting that type I interferon may not be significant in resistance SFTSV infection in humans and it may play an import role in cytokine storm. -
It Takes Two to Tango
HIGHLIGHTS IMMUNOTHERAPY It takes two to tango Much of the recent work on the development of active, specific immunotherapy of cancer has focused on the induction of CD8+ cytotoxic T-lymphocyte (CTL) responses, and several studies have shown that it is possible to stimulate tumour-specific CTLs using dendritic cells (DCs) that are loaded with tumour antigens. But CD4+ T-helper type 1 (TH1) cells are also important day of vaccination and loaded with various So, the results from this Phase I trial provide components of effective immune responses. MHC class-I- and -II-restricted peptides. convincing evidence that cryopreserved DCs In this study, Schuler–Thurner and Patients with incurable melanoma were can induce TH1 responses against tumour colleagues provide the first evidence that DCs treated with five biweekly vaccinations of antigens without significant toxicity, and it that are loaded with tumour-specific peptides DCs, followed by assessment one month also encourages further development of can rapidly induce TH1 responses in cancer after the final vaccination. DC-based vaccination technology. patients that are readily detectable ex vivo. The results showed that the vaccination Elaine Bell References and links The DCs that were used for vaccination protocol induced a rapid TH1 response in in this study were derived from blood patients, both to a control immunizing antigen ORIGINAL RESEARCH PAPER Schuler–Thurner, B. et al. Rapid induction of tumor-specific type 1 T helper cells in monocytes that were matured ex vivo using and also to defined MHC class-II-restricted metastatic melanoma patients by vaccination with mature, a defined cocktail (consisting of interleukin tumour antigens. -
MST1 Is a Key Regulator of Beta Cell Apoptosis and Dysfunction in Diabetes
ARTICLES MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes Amin Ardestani1, Federico Paroni1,6, Zahra Azizi1,6, Supreet Kaur1,6, Vrushali Khobragade1, Ting Yuan1, Thomas Frogne2, Wufan Tao3, Jose Oberholzer4, Francois Pattou5, Julie Kerr Conte5 & Kathrin Maedler1 Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20–like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets and specifically induced the mitochondrial-dependent pathway of apoptosis through upregulation of the BCL-2 homology-3 (BH3)-only protein BIM. MST1 directly phosphorylated the beta cell transcription factor PDX1 at T11, resulting in the latter’s ubiquitination and degradation and thus in impaired insulin secretion. MST1 deficiency completely restored normoglycemia, beta cell function and survival in vitro and in vivo. We show MST1 as a proapoptotic kinase and key mediator of apoptotic signaling and beta cell dysfunction and suggest that it may serve as target for the development of new therapies for diabetes. Pancreatic beta cell death is the fundamental cause of type 1 diabetes of events, which makes the initiation of beta cell death complex and (T1D) and a contributing factor to the reduced beta cell mass in type 2 its blockade difficult to successfully achieve in vivo. -
1 ICAM3-Fc Outperforms Receptor-Specific Antibodies
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 10 April 2019 doi:10.20944/preprints201904.0118.v1 Peer-reviewed version available at Molecules 2019, 24, 1825; doi:10.3390/molecules24091825 ICAM3-Fc outperforms receptor-specific antibodies targeted nanoparticles to dendritic cells for cross-presentation Luis J. Cruz,1* Paul J. Tacken,2 Johan S. van der Schoot,2 Felix Rueda,3 Ruurd Torensma,2 Carl G. Figdor2* 1Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. 2Department of Tumor Immunology, Radboud Insititute for Molecular Life Sciences, Radboud University Medical Center, Postbox 9101, 6500 HB Nijmegen, The Netherlands. 3Department of Biochemistry and Molecular Biology, University of Barcelona, Diagonal 643, 08028 Barcelona, Spain. Running title: ICAM3-Fc- versus antibody-targeted NP vaccines to human DCs Keywords: Delivery system; nanoparticle; targeting. AUTHOR INFORMATION Corresponding Author *Dr. Luis J. Cruz Translational Nanobiomaterials and Imaging, Department of Radiology, Bldg.1, C5-60. Leiden University Medical Center, Albinusdreef 2 2333 ZA Leiden, The Netherlands Tel: +31 71 5263025 Email: [email protected] *Prof. Dr. Carl G. Figdor Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Postbox 9101, 6500 HB Nijmegen, The Netherlands. Fax: +31-24-3540339; Tel.: +31-24-3617600; E-mail: [email protected] 1 © 2019 by the author(s). Distributed -
Regulation of Calreticulin–Major Histocompatibility Complex (MHC) Class I Interactions by ATP
Regulation of calreticulin–major histocompatibility complex (MHC) class I interactions by ATP Sanjeeva Joseph Wijeyesakerea, Jessica K. Gagnonb, Karunesh Arorab, Charles L. Brooks IIIb, and Malini Raghavana,1 aDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and bDepartment of Chemistry, University of Michigan, Ann Arbor, MI 48109 Edited by Peter Cresswell, Yale University School of Medicine, New Haven, CT, and approved September 1, 2015 (received for review May 26, 2015) The MHC class I peptide loading complex (PLC) facilitates the assembly computational methods validated by experimental approaches, we of MHC class I molecules with peptides, but factors that regulate the identify residues within the globular domain of calreticulin that stability and dynamics of the assembly complex are largely unchar- are important for ATP binding and ATPase activity. Based on acterized. Based on initial findings that ATP, in addition to MHC class further investigations into the functional effects of calreticulin I-specific peptide, is able to induce MHC class I dissociation from the mutants with deficiencies in ATP interactions, we elucidate a key PLC, we investigated the interaction of ATP with the chaperone role for ATP in the regulation of PLC dynamics and the in- calreticulin, an endoplasmic reticulum (ER) luminal, calcium-bind- teraction of calreticulin with other cellular proteins. ing component of the PLC that is known to bind ATP. We combined computational and experimental measurements to identify residues Results within the globular domain of calreticulin, in proximity to the high- ATP Destabilizes the PLC, Promoting MHC Class I Release. Calreticulin- affinity calcium-binding site, that are important for high-affinity ATP deficient mouse embryonic fibroblasts (MEFs) reconstituted binding and for ATPase activity. -
Physical Exercise and Myokines: Relationships with Sarcopenia and Cardiovascular Complications
International Journal of Molecular Sciences Review Physical Exercise and Myokines: Relationships with Sarcopenia and Cardiovascular Complications Sandra Maria Barbalho 1,2,3,* , Uri Adrian Prync Flato 1,2 , Ricardo José Tofano 1,2, Ricardo de Alvares Goulart 1, Elen Landgraf Guiguer 1,2,3 , Cláudia Rucco P. Detregiachi 1 , Daniela Vieira Buchaim 1,4, Adriano Cressoni Araújo 1,2 , Rogério Leone Buchaim 1,5, Fábio Tadeu Rodrigues Reina 1, Piero Biteli 1, Daniela O. B. Rodrigues Reina 1 and Marcelo Dib Bechara 2 1 Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil; urifl[email protected] (U.A.P.F.); [email protected] (R.J.T.); [email protected] (R.d.A.G.); [email protected] (E.L.G.); [email protected] (C.R.P.D.); [email protected] (D.V.B.); [email protected] (A.C.A.); [email protected] (R.L.B.); [email protected] (F.T.R.R.); [email protected] (P.B.); [email protected] (D.O.B.R.R.) 2 School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília 17506-000, São Paulo, Brazil; [email protected] 3 Department of Biochemistry and Nutrition, Food Technology School, Marília 17525-902, São Paulo, Brazil 4 Medical School, University Center of Adamantina (UniFAI), Adamantina 17800-000, São Paulo, Brazil 5 Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (FOB–USP), Alameda Doutor Octávio Pinheiro Brisolla, 9-75, Bauru 17012901, São Paulo, Brazil * Correspondence: [email protected]; Tel.: +55-14-99655-3190 Received: 6 May 2020; Accepted: 19 May 2020; Published: 20 May 2020 Abstract: Skeletal muscle is capable of secreting different factors in order to communicate with other tissues. -
CD154 Costimulation Shifts the Local T-Cell Receptor
CD154 Costimulation Shifts the Local T-Cell Receptor Repertoire Not Only During Thymic Selection but Also During Peripheral T-Dependent Humoral Immune Responses Anke Faehnrich, Sebastian Klein, Arnauld Serge, Christin Nyhoegen, Sabrina Kombrink, Steffen Moeller, Karsten Keller, Juergen Westermann, Kathrin Kalies To cite this version: Anke Faehnrich, Sebastian Klein, Arnauld Serge, Christin Nyhoegen, Sabrina Kombrink, et al.. CD154 Costimulation Shifts the Local T-Cell Receptor Repertoire Not Only During Thymic Selection but Also During Peripheral T-Dependent Humoral Immune Responses. Frontiers in Immunology, Frontiers, 2018, 9, 10.3389/fimmu.2018.01019. hal-02143668 HAL Id: hal-02143668 https://hal-amu.archives-ouvertes.fr/hal-02143668 Submitted on 26 Nov 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License ORIGINAL RESEARCH published: 17 May 2018 doi: 10.3389/fimmu.2018.01019 CD154 Costimulation Shifts the Local T-Cell Receptor Repertoire Not Only During Thymic Selection -
Efficient Elimination of Primary B-ALL Cells in Vitro and in Vivo Using A
Open access Original research J Immunother Cancer: first published as 10.1136/jitc-2020-000896 on 11 August 2020. Downloaded from Efficient elimination of primary B- ALL cells in vitro and in vivo using a novel 4- 1BB- based CAR targeting a membrane- distal CD22 epitope 1 1 1 Talia Velasco- Hernandez , Samanta Romina Zanetti , Heleia Roca- Ho, Francisco Gutierrez- Aguera,1 Paolo Petazzi,1 Diego Sánchez- Martínez,1 Oscar Molina,1 Matteo Libero Baroni,1 Jose Luis Fuster,2 Paola Ballerini,3 1,4 5 6,7 Clara Bueno, Narcis Fernandez- Fuentes, Pablo Engel , Pablo Menendez1,4,7,8 To cite: Velasco- Hernandez T, ABSTRACT BACKGROUND Zanetti SR, Roca- Ho H, et al. Background There are few therapeutic options available for B-cell acute lymphoblastic leukemia (B-ALL) Efficient elimination of primary patients with B- cell acute lymphoblastic leukemia (B- ALL) is an aggressive cancer, diagnosed at any age B- ALL cells in vitro and in vivo – using a novel 4- 1BB- based relapsing as CD19 either after chemotherapy or CD19- throughout the lifespan of an individual, CAR targeting a membrane- targeted immunotherapies. CD22- chimeric antigen receptor being the most common malignancy in distal CD22 epitope. Journal (CAR) T cells represent an attractive addition to CD19- CAR children.1 Despite current 5-year disease- + – for ImmunoTherapy of Cancer T cell therapy because they will target both CD22 CD19 free survival rates of ~80%, refractory and 2020;8:e000896. doi:10.1136/ B- ALL relapses and CD19– preleukemic cells. However, jitc-2020-000896 relapsed (R/R) patients have a dismal prog- the immune escape mechanisms from CD22- CAR T cells, nosis.2–7 Adult B- ALL is less frequent, but is and the potential contribution of the epitope binding of the commonly associated with an unfavorable ► Additional material is anti-CD22 single-chain variable fragment (scFv) remain published online only. -
Cell Biology from an Immune Perspective in This Lecture We Will
Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Cell Biology from an Immune Perspective In this lecture we will very briefly review some aspects of cell biology which are required as background knowledge in order to understand how the immune system works. These will include: 1. A brief overview of protein trafficking 2. Signal transduction 3. The cell cycle Some of these issues will be treated in greater depth in later lectures. Protein Trafficking/The Secretory Pathway: From an immune perspective the secretory compartment and structures enclosed by vesicles are “seen” in different ways from proteins that reside in the cytosol or the nucleus. We will briefly review the secretory and endocytic pathways and discuss the biogenesis of membrane proteins. Some of the issues that will be discussed are summarized in Figures 1-3. Early endosomes Late endosomes Lysosomes Golgi Vesiculo-Tubular Compartment ER Figure 1. An overview of the secretory pathway Early endosomes Late endosomes Multivesicular and multilamellar bodies Golgi ER Proteasomes Figure 2. Protein degradation occurs mainly in lysosomes and proteasomes Proteins that enter the cell from the environment are primarily degraded in lysosomes. Most cytosolic and nuclear proteins are degraded in organelles called proteasomes. Intriguingly these two sites of degradation are each functionally linked to distinct antigen presentation pathways, different kinds of MHC molecules and the activation of different categories of T cells. Integral membrane proteins maybe inserted into the membrane in a number of ways, the two most common of these ways being considered in Figure 3. -
Expression of Lymphocyte-Endothelial Receptor-Ligand Pairs, Α4β7
856 Gut 1999;45:856–863 Expression of lymphocyte-endothelial receptor-ligand pairs, á4â7/MAdCAM-1 and Gut: first published as 10.1136/gut.45.6.856 on 1 December 1999. Downloaded from OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease H S Souza, C C S Elia, J Spencer, T T MacDonald Abstract sion molecules and the synthesis and release of Background—The interaction between chemokines and cytokines have been impli- leucocytes and vascular endothelial cells is cated in the recruitment and emigration of essential for leucocyte migration into inflammatory cells from the circulation to sites inflammatory sites. of inflammation. In the gut, increased endothe- Aims—To study the local expression of the lial cell expression of intercellular adhesion pairs of complementary molecules, á4â7/ molecule (ICAM) 1, P-selectin, E-selectin, and mucosal addressin cell adhesion molecule mucosal addressin cell adhesion molecule (MAdCAM-1) and OX40/OX40 ligand in (MAdCAM-1) has been observed in the the lamina propria of the colon and inflamed colonic mucosa of patients with 1–5 jejunum of patients with inflammatory inflammatory bowel diseases. The increased bowel disease. expression of adhesion molecules on endothe- Methods—Ten patients with active ulcera- lial cells is mediated by proinflammatory tive colitis (UC), nine with active Crohn’s cytokines such as interleukin (IL) 1 and 6–8 disease (CD), and seven irritable bowel tumour necrosis factor á (TNF-á) which are syndrome (IBS) controls were submitted expressed at increased concentrations in the to endoscopic and peroral jejunal biop- inflamed mucosa of patients with inflammatory 9–13 sies. -
Antigen-Specific Induced Foxp3 Regulatory T Cells Are Generated
Antigen-specific induced Foxp3+ regulatory T cells are generated following CD40/CD154 blockade Ivana R. Ferrer, Maylene E. Wagener, Minqing Song, Allan D. Kirk, Christian P. Larsen, and Mandy L. Ford1 Emory Transplant Center and Department of Surgery, Emory University, Atlanta, GA 30322 Edited by James P. Allison, Memorial Sloan-Kettering Cancer Center, New York, NY, and approved November 4, 2011 (received for review April 7, 2011) Blockade of the CD40/CD154 pathway potently attenuates T-cell in vivo accumulation of Treg and deletion of graft-specific ef- responses in models of autoimmunity, inflammation, and trans- fectors after CD40/CD154 blockade has not been investigated. plantation. Indeed, CD40 pathway blockade remains one of the To address these questions, we used an ovalbumin (OVA)- most powerful methods of prolonging graft survival in models of expressing transgenic mouse model (20), which allowed us to di- + + transplantation. But despite this effectiveness, the cellular and rectly track both donor-reactive CD4 and CD8 T-cell responses molecular mechanisms underlying the protective effects of CD40 simultaneously over time. Although previous studies have used pathway blockade are incompletely understood. Furthermore, the transgenic models to assess the degree of T-cell deletion after CD154/CD40 blockade (16, 21), none has systematically inter- relative contributions of deletion, anergy, and regulation have not + been measured in a model in which donor-reactive CD4+ and CD8+ rogated the impact of anti-CD154 on the kinetics of both CD4 and CD8+ T-cell deletion and acquisition of effector function. T-cell responses can be assessed simultaneously. To investigate the fi Our results indicated that although CD40/CD154 blockade alone impact of CD40/CD154 pathway blockade on graft-speci c T-cell delayed donor-reactive CD4+ and CD8+ T-cell expansion and responses, a transgenic mouse model was used in which recipients differentiation, the addition of DST was required for antigen- fi + + containing ovalbumin-speci cCD4 and CD8 TCR transgenic T specific T-cell deletion. -
Human CD154 (CD40 Ligand) Recombinant Protein Catalog Number: 14-8502 Also Known As:CD40L, CD40-L RUO: for Research Use Only
Human CD154 (CD40 Ligand) Recombinant Protein Catalog Number: 14-8502 Also Known As:CD40L, CD40-L RUO: For Research Use Only Product Information Contents: Human CD154 (CD40 Ligand) Recombinant Protein Formulation: Sterile liquid: phosphate buffered saline, pH 7.2, Catalog Number: 14-8502 1.0% BSA. 0.22 µm filtered. Handling Conditions: For best recovery, quick-spin vial prior to Temperature Limitation: Store at less than or equal to -70°C. opening. Use in a sterile environment Batch Code: Refer to Vial Source: E. coli Use By: Refer to Vial Purity: Greater than 98%, as determined by SDS-PAGE Endotoxin Level: Less than 0.01 ng/ug cytokine as determined by the LAL assay. Bioactivity: The ED50 measured in a T-47D cell line proliferation assay is typically 40 ng/ml, corresponding to a specific activity of approximately 2.5 x104 Units/mg. Description CD40 ligand, (CD40L, also known as CD154, TRAP or gp39) is a membrane glycoprotein expressed on activated CD4+ T-cells, NK cells, mast cells, basophils and eosinophils. The CD40-CD40L interaction stimulates B cell immune response which includes cell surface antigen expression, cell cycle activation, Ig isotype switching, Ig secretion and memory generation. The CD40-CD40L interaction also plays important roles in monocyte and dendritic cell activation, T-cell co-stimulation and cytokine production. It has been reported that the CD40-CD40L interaction is involved in the pathogenesis of amyloid pathology in Alzheimer disease. Recombinant Human CD40L produced in E.Coli is a non-glycosylated, polypeptide containing 149 amino acids and having a molecular mass of 16 kDa.