DOCSLIB.ORG

CCL3 Augments Antitumor Responses in CT26 by Enhancing Cellular

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
CCL3 Augments Antitumor Responses in CT26 by Enhancing Cellular CCL3 AUGMENTS ANTITUMOR RESPONSES IN CT26 BY ENHANCING CELLULAR TRAFFICKING AND INTERFERON-GAMMA EXPRESSION by FREDERICK ALLEN Submitted in Partial Fulfilment of the Requirements for the Degree of Doctor of Philosophy Dissertation Advisor: Alex Y. Huang, M.D., Ph.D. Department of Pathology Immunology Training Program CASE WESTERN RESERVE UNIVERSITY January 2018 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Frederick Allen Candidate for the Ph.D. degree Committee Chair Pamela Wearsch, Ph.D. Committee Member Pushpa Pandiyan, Ph.D. Committee Member Clive Hamlin, Ph.D. Committee Member and Advisor Alex Y. Huang, M.D., Ph.D. Date of Thesis Defense November 13, 2017 *We also certify that written approval has been obtained for any proprietary material contained therein. 2 TABLE OF CONTENTS Acknowlegment ………………………………………………………………………………………. 10 List of major abbreviations ............................................................................................... 12 Abstract ............................................................................................................................. 13 Chapter I - Introduction to the major tissue, cellular and cytokine components involved in the CCL3-expressing CT26 tumor microenvironment ..................................................... 15 A brief history of immunotherapy ................................................................................. 16 The tumor microenvironment – from tumor escape to indirect immunomodulation .... 17 Cytokines ....................................................................................................................... 18 Chemokines ................................................................................................................... 19 Macrophage inflammatory protein 1 �, 1�, and rantes ................................................. 20 CCL3 and CCL4 – Overview .................................................................................... 20 CCL3 and CCL4 ........................................................................................................ 21 CCL3 and CCL5 ........................................................................................................ 23 Lymph node .................................................................................................................. 24 Primary and secondary immune organs – general overview ..................................... 24 Chemokine influence on lymph node cellular trafficking dynamics ......................... 25 Interferon-gamma .......................................................................................................... 25 Natural killer cells ......................................................................................................... 26 Dendritic cells ............................................................................................................... 28 Dendritic cells – Overview ........................................................................................ 28 Dendritic cell maturation ........................................................................................... 29 3 Chapter II - Unique Transcompartmental Bridge: Antigen-Presenting Cells Sampling across Endothelial and Mucosal Barriers (Review) .......................................................... 31 Abstract ......................................................................................................................... 32 Introduction ................................................................................................................... 33 Gut mucosa: apc transepithelial extensions in lamina propria and peyer’s patch ......... 34 Information exchange between LN conduits and follicular DCs (FDCs) ..................... 39 LN-resident and migratory DCs interact directly with lymphatic conduits and HEVs 41 CD169+ Macs extend processes from subcapsular sinus into ln follicular zones to assist in activating the adaptive humoral response .................................................................. 42 Local LN DCs extend dendritic processes into lymphatic fluid to initiate early T cell activation ........................................................................................................................ 43 APC extensions in other anatomical compartments: airway lumen and CNS vessels .. 44 Concluding remarks ...................................................................................................... 46 Chapter III - CCL3 enhances antitumor immune priming in the lymph node via IFN� with dependency on NK cells ................................................................................ 53 Abstract ......................................................................................................................... 54 Introduction ................................................................................................................... 55 Materials and methods .................................................................................................. 57 Results ........................................................................................................................... 61 aCCL3 suppresses tumor growth and promotes tumor rejection .............................. 61 aCCL3 augments T cell activation by enhancing leukocyte migration to the TDLN 62 aCCL3 bolsters the intracellular production of IFN�+ cells in the TDLN ................ 64 L3TU enhanced leukocyte accumulation is dependent on CCL3 but not NK cells .. 65 4 NK cells, but not CD103+ CD11c+ DCs are important for driving the production of IFN�-induced chemokines CXCL9 and CXCL10 in the TDLN ............................... 66 Exposure of BMDCs to rCCL3 enhances Ag-specific T cell proliferation ............... 66 Discussion ..................................................................................................................... 67 Chapter IV - CCL3 augments tumor rejection and enhances CD8+ T cell infiltration through NK and CD103+ dendritic cell recruitment via IFN� .......................................... 89 Abstract ......................................................................................................................... 90 Introduction ................................................................................................................... 91 Material and methods .................................................................................................... 93 Results ........................................................................................................................... 97 CCL3 facilitates tumor rejection via thymic-dependent and thymic-independent mechanisms ............................................................................................................... 97 CCL3 enhances CD4+ and CD8+ T cell infiltration to the primary tumor site .......... 98 CCL3 recruits NK cells to promote CD103+ DCs infiltration and support T cell function within the primary tumor ............................................................................. 99 Subcutaneously administered rCCL3 significantly slowed tumor growth in established tumors ................................................................................................... 101 Discussion ................................................................................................................... 102 Chapter V – Conclusion .................................................................................................. 126 The significance of IFN� in promoting early and late proinflammatory responses with L3TU ............................................................................................................................ 130 Dendritic cell maturation in the tumor microenvironment ......................................... 134 5 The interaction of CCL3, interferon-gamma, and CCL5 in the L3TU tumor microenvironement ...................................................................................................... 137 The dual role of IFN� in tumors .............................................................................. 137 Identifying and targeting tumor intrinsic pathways related to IFN� and WNT/�- catenin, to enhance the constitutive expression CCL3 and tumor rejection ............ 139 Thoughts on the therapeutic application of using high dose recombinant ccl3 .............. 142 Final thoughts ................................................................................................................. 144 Bibliography ................................................................................................................... 145 6 LIST OF FIGURES Figure 1 - Different models of TE and antigen uptake by LP APC .................................. 47 Figure 2 - Overview of LN APC positioning for TE sampling ........................................ 49 Figure 3 - Activated DCs reside near HEV after migrating from the periphery ............... 50 Figure 4 - LN DCs and Macs extend processes into the medullary sinus to directly sample lymph-borne antigen ......................................................................................................... 51 Figure 5 - Lung DCs sample airway pathogens via TEs .................................................. 52 Figure 6 - Autologous or recombinant CCL3 slows tumor growth and promotes tumor rejection ............................................................................................................................
Load more

Recommended publications
  • Differentiation and Bone Resorption Role of CX3CL1/Fractalkine In
    Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption Keiichi Koizumi, Yurika Saitoh, Takayuki Minami, Nobuhiro Takeno, Koichi Tsuneyama, Tatsuro Miyahara, This information is current as Takashi Nakayama, Hiroaki Sakurai, Yasuo Takano, Miyuki of September 29, 2021. Nishimura, Toshio Imai, Osamu Yoshie and Ikuo Saiki J Immunol published online 18 November 2009 http://www.jimmunol.org/content/early/2009/11/18/jimmuno l.0803627.citation Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 29, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published November 18, 2009, doi:10.4049/jimmunol.0803627 The Journal of Immunology Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption1 Keiichi Koizumi,2* Yurika Saitoh,* Takayuki Minami,* Nobuhiro Takeno,* Koichi Tsuneyama,†‡ Tatsuro Miyahara,§ Takashi Nakayama,¶ Hiroaki Sakurai,*† Yasuo Takano,‡ Miyuki Nishimura,ʈ Toshio Imai,ʈ Osamu Yoshie,¶ and Ikuo Saiki*† The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for osteoclast dif- ferentiation.
    [Show full text]
  • Acting on the CCR1 Receptor Mediates Neutrophil Migration in Immune Inflammation Via Sequential ␣ Release of TNF- and LTB4 Cleber D
    MIP-1␣[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential ␣ release of TNF- and LTB4 Cleber D. L. Ramos,* Claudio Canetti,*,† Janeusa T. Souto,‡,§ Joa˜ o S. Silva,‡ Cory M. Hogaboam,¶ Sergio H. Ferreira,* and Fernando Q. Cunha*,1 Departments of *Pharmacology and ‡Biochemistry and Immunology, School of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Brazil; §Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Natal, RN, Brazil; and †Division of Pulmonary & Critical Care Medicine and ¶Department of Pathology, University of Michigan, Ann Arbor Abstract: In the present study, we investigated nists might have a therapeutic potential. J. Leukoc. the involvement of macrophage-inflammatory pro- Biol. 78: 167–177; 2005. tein-1␣ (MIP-1␣)[CC chemokine ligand 3 (CCL3)], MIP-1␤[CCL4], regulated on activation, normal Key Words: chemokines ⅐ chemokine receptors ⅐ chemotaxis T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- INTRODUCTION ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor Neutrophil migration is a complex process, which results ␣ ␣ mainly from the release of neutrophil chemotactic factors by (TNF- ) and leukotriene B4 (LTB4). Herein, we show increased mRNA expression for MIP- resident cells, inducing rolling and adhesion of neutrophils on 1␣[CCL3], MIP-1␤[CCL4], RANTES[CCL5], and endothelial cells, followed by their transmigration to the ex- travascular space [1, 2]. Apart from its importance in host CCR1 in peritoneal cells harvested from OVA-chal- defense, the migration of neutrophils to the inflammatory site lenged, immunized mice, as well as MIP-1␣[CCL3] is, at least in part, responsible for tissue damage observed in and RANTES[CCL5] but not MIP-1␤[CCL4] proteins several inflammatory diseases such as rheumatoid arthritis, in the peritoneal exudates.
    [Show full text]
  • 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.
    [Show full text]
  • Haplotypes in CCR5-CCR2, CCL3 and CCL5 Are Associated with Natural Resistance to HIV-1 Infection in a Colombian Cohort Jorge A
    Biomédica 2017;37:267-73 Haplotypes associated with resistance to HIV-1 doi: http://dx.doi.org/10.7705/biomedica.v37i3.3237 BRIEF COMMUNICATION Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort Jorge A. Vega1,2,3, Simón Villegas-Ospina1, Wbeimar Aguilar-Jiménez1, María T. Rugeles1, Gabriel Bedoya3, Wildeman Zapata1,4 1 Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia 2 Laboratorio de Genética, Dirección Regional Noroccidente, Instituto Nacional de Medicina Legal y Ciencias Forenses, Medellín, Colombia 3 Genética Molecular, Instituto de Biología, Universidad de Antioquia, Medellín, Colombia 4 Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia Introduction: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. Objective: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Materials and methods: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p’ value <0.05 after Bonferroni correction was considered significant. Results: Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility.
    [Show full text]
  • Ccl17-Dependent Release of Ccl3 Restrains Regulatory T Cells Thereby Aggravating Atherosclerosis
    From the Institute for Cardiovascular Prevention (IPEK) of the Ludwig-Maximilians-Universität München Director: Univ.-Prof. Dr. med. Christian Weber Ccl17-dependent release of Ccl3 restrains regulatory T cells thereby aggravating atherosclerosis Dissertation zum Erwerb des Doctor of Philosophy (Ph.D.) an der Medizinischen Fakultät der Ludwig-Maximilians-Universität München Submitted by M.Sc. Carlos Neideck from Taió in Santa Catarina, Brazil on 21.03.2018 Supervisor: Prof. Dr. med. Christian Weber Second evaluator: Prof. Dr. rer. nat. Jürgen Bernhagen Dean: Prof. Dr. Reinhard Hickel Date of oral defense: 23.07.2018 Affidavit Neideck, Carlos ______________________________________________________________________ Name, Surname ______________________________________________________________________ Street ______________________________________________________________________ Zip Code, Town ______________________________________________________________________ Country I hereby declare, that the submitted thesis entitled: “Ccl17-dependent release of Ccl3 restrains regulatory T cells thereby aggravating atherosclerosis.” is my own work. I have only used the sources indicated and have not made unauthorized use of services of a third party. Where the work of others has been quoted or reproduced, the source is always given. I further declare that the submitted thesis or parts thereof have not been presented as part of an examination degree to any other university. Munich, 25.07.2018 Carlos Neideck Place, date Signature doctoral candidate Confirmation
    [Show full text]
  • CCL5 T Cells to CCL3 and + Human Naive CD4 Associated with The
    An Abortive Ligand-Induced Activation of CCR1-Mediated Downstream Signaling Event and a Deficiency of CCR5 Expression Are Associated with the Hyporesponsiveness of This information is current as Human Naive CD4 + T Cells to CCL3 and of October 3, 2021. CCL5 Katsuaki Sato, Hiroshi Kawasaki, Chikao Morimoto, Naohide Yamashima and Takami Matsuyama J Immunol 2002; 168:6263-6272; ; Downloaded from doi: 10.4049/jimmunol.168.12.6263 http://www.jimmunol.org/content/168/12/6263 References This article cites 44 articles, 26 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/168/12/6263.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 3, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology An Abortive Ligand-Induced Activation of CCR1-Mediated Downstream Signaling Event and a Deficiency of CCR5 Expression Are Associated with the Hyporesponsiveness of Human Naive CD4؉ T Cells to CCL3 and CCL51 Katsuaki Sato,2* Hiroshi Kawasaki,† Chikao Morimoto,† Naohide Yamashima,‡ and Takami Matsuyama* .Human memory CD4؉ T cells respond better to inflammatory CCLs/CC chemokines, CCL3 and CCL5, than naive CD4؉ T cells We analyzed the regulatory mechanism underlying this difference.
    [Show full text]
  • PM Coronary Artery Atherosclerosis 8740 Online
    RnDSy-lu-2945 Atherosclerosis Disease Progression Healthy Endothelial Damage Cellular uptake of lipids Intracellular cholesterol metabolism LDL oxidation Reverse cholesterol transport Foam cell development LDL OXIDATION Minimally modified (mmLDL) to oxidized (oxLDL) Agents Substrates Products Lipoxygenase ApoA1,ApoB Aldehydes (HNE,MDA) Myeloperoxidase Cholesteryl esters Free fatty acids NADPH oxidase Phospholipids Lipid hydroperoxides Phospholipases Polyunsaturated fatty acids Lysophosphatidic acid (LPA) Xanthine oxidase Lysophosphatidyl choline (LPC) TBARS Cathepsin K IFN-γ Prostaglandin E2 CCL2,3,4,5,8,11,19,20,22 IL-6,10,17,18 PLA2G7 CX3CL1 MMPs Thromboxane A2 CXCL2,8,9,10,16 Prostaglandin D2 TNF-α NITRIC OXIDE EFFECTS Vasoconstriction DC-SIGN CD11b CCL2 Fcγ RII/III Endothelial permeability CD14 IL-12,23 Angiogenesis NO IFN-γ R1 α Platelet aggregation TNF- AT1 SMC proliferation RAGE TLR4-MD2-CD14 PDGF R Leukocyte adhesion ApoA1 LOX-1 Dendritic DEC205 Cell RAGE SREBP HMG Co A PTGER2 CD11c Low Sterol Conditions SCAP SREBP Cholesterol MARCO Reductase CD36 Cholesteryl esters Activation Synthesis GM-CSF INSIG LDL R TLR4 ligation Triglycerides CX3CR1 γ LOX-1 Monocyte LOX-1 RAGE Fc RII/III LXRα or β ABCA1, G1 NO TLR2 Phospholipids P-Selectin Integrin α4β1 High Sterol Conditions ROR PLTP, CETP, LPL E-Selectin CCR5 + eNOS ApoE2,C1,C2,C4 Integrin αLβ2 CD36 Oxysterols CCR2 IDOL LDL PGI2 Macrophage degradation (M1 polarized) SR-A TLR4-MD2-CD14 CCL2,3,4,5,8,11,15,19,20,22 IL-6,10,15,17,18,23 CXCL1,2,3,5,8,9,10,11,13,16 Cathepsin K Mature
    [Show full text]
  • COVID-19: Mechanisms of Vaccination and Immunity
    Review COVID-19: Mechanisms of Vaccination and Immunity Daniel E. Speiser 1,* and Martin F. Bachmann 2,3,4,* 1 Department of Oncology, University Hospital and University of Lausanne, 1066 Lausanne, Switzerland 2 International Immunology Centre, Anhui Agricultural University, Hefei 230036, China 3 Department of Rheumatology, Immunology and Allergology, Inselspital, University of Bern, 3010 Bern, Switzerland 4 Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland * Correspondence: [email protected] (D.E.S.); [email protected] (M.F.B.) Received: 2 July 2020; Accepted: 20 July 2020; Published: 22 July 2020 Abstract: Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy. Keywords: SARS-CoV-2; COVID-19; nucleic acid tests; serology; vaccination; immunity 1. Introduction The COVID-19 pandemic holds great challenges for which the world is only partially prepared [1]. SARS-CoV-2 combines serious pathogenicity with high infectivity. The latter is enhanced by the fact that asymptomatic and pre-symptomatic individuals can transmit the virus, in contrast to SARS-CoV-1 and MERS-CoV, which were transmitted by symptomatic patients and could be contained more efficiently [2,3].
    [Show full text]
  • CXCL4/Platelet Factor 4 Is an Agonist of CCR1 and Drives Human Monocyte Migration
    This is a repository copy of CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/132464/ Version: Published Version Article: Fox, James Martin orcid.org/0000-0002-2473-7029, Kausar, Fahima, Day, Amy et al. (7 more authors) (2018) CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. Scientific Reports. 9466. ISSN 2045-2322 Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ www.nature.com/scientificreports OPEN CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration Received: 10 March 2016 James M. Fox 1,3, Fahima Kausar1, Amy Day1, Michael Osborne1, Khansa Hussain1, Accepted: 5 June 2018 Anja Mueller1,4, Jessica Lin1, Tomoko Tsuchiya 2, Shiro Kanegasaki2 & James E. Pease1 Published: xx xx xxxx Activated platelets release micromolar concentrations of the chemokine CXCL4/Platelet Factor-4. Deposition of CXCL4 onto the vascular endothelium is involved in atherosclerosis, facilitating monocyte arrest and recruitment by an as yet, unidentified receptor.
    [Show full text]
  • The CCL7-CCL2-CCR2 Axis Regulates IL-4 Production in Lungs and Fungal Immunity Wendy A
    The CCL7-CCL2-CCR2 Axis Regulates IL-4 Production in Lungs and Fungal Immunity Wendy A. Szymczak and George S. Deepe, Jr This information is current as J Immunol 2009; 183:1964-1974; Prepublished online 8 July of September 29, 2021. 2009; doi: 10.4049/jimmunol.0901316 http://www.jimmunol.org/content/183/3/1964 Downloaded from References This article cites 57 articles, 33 of which you can access for free at: http://www.jimmunol.org/content/183/3/1964.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 29, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology The CCL7-CCL2-CCR2 Axis Regulates IL-4 Production in Lungs and Fungal Immunity1 Wendy A. Szymczak*† and George S. Deepe, Jr.2*‡ Expression of the chemokine receptor CCR2 can be detrimental or beneficial for infection resolution.
    [Show full text]
  • Mechanisms of Dysregulated Humoral and Cellular Immunity by SARS-Cov-2
    pathogens Review Mechanisms of Dysregulated Humoral and Cellular Immunity by SARS-CoV-2 Nima Taefehshokr 1 , Sina Taefehshokr 2 and Bryan Heit 1,3,* 1 Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, ON N0M 2N0, Canada; [email protected] 2 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51368, Iran; [email protected] 3 Robarts Research Institute, London, ON N6A 5K8, Canada * Correspondence: [email protected]; Tel.: +1-519-661-3407 Received: 10 November 2020; Accepted: 6 December 2020; Published: 8 December 2020 Abstract: The current coronavirus disease 2019 (COVID-19) pandemic, a disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was first identified in December 2019 in China, and has led to thousands of mortalities globally each day. While the innate immune response serves as the first line of defense, viral clearance requires activation of adaptive immunity, which employs B and T cells to provide sanitizing immunity. SARS-CoV-2 has a potent arsenal of mechanisms used to counter this adaptive immune response through processes, such as T cells depletion and T cell exhaustion. These phenomena are most often observed in severe SARS-CoV-2 patients, pointing towards a link between T cell function and disease severity. Moreover, neutralizing antibody titers and memory B cell responses may be short lived in many SARS-CoV-2 patients, potentially exposing these patients to re-infection. In this review, we discuss our current understanding of B and T cells immune responses and activity in SARS-CoV-2 pathogenesis.
    [Show full text]
  • CX3CL1 System in the Cross-Talk Between Chronic Lymphocytic Leukemia Cells and Tumor Microenvironment
    Leukemia (2011) 25, 1268–1277 & 2011 Macmillan Publishers Limited All rights reserved 0887-6924/11 www.nature.com/leu ORIGINAL ARTICLE A novel role of the CX3CR1/CX3CL1 system in the cross-talk between chronic lymphocytic leukemia cells and tumor microenvironment E Ferretti1, M Bertolotto2, S Deaglio3, C Tripodo4, D Ribatti5, V Audrito3, F Blengio6, S Matis7, S Zupo8, D Rossi9, L Ottonello2, G Gaidano9, F Malavasi10, V Pistoia1,11 and A Corcione1,11 1Laboratory of Oncology, IRCCS G. Gaslini, Genova, Italy; 2Laboratory of Phagocyte Physiopathology and Inflammation, Department of Internal Medicine, University of Genova, Genova, Italy; 3Department of Genetics, Biology & Biochemistry, Human Genetics Foundation (HuGeF), University of Torino, Torino, Italy; 4Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo, Palermo, Italy; 5Department of Human Anatomy and Histology, University of Bari, Bari, Italy; 6Laboratory of Molecular Biology, Gaslini Institute, Genova, Italy; 7Medical Oncology C, National Cancer Research Institute, Genova, Italy; 8Laboratory of Diagnostics of Lymphoproliferative Disorders, National Cancer Research Institute, Genova, Italy; 9Division of Hematology, Department of Clinical and Experimental Medicine, Amedeo Avogadro, University of Eastern Piedmont, Novara, Italy and 10Department of Genetics, Biology & Biochemistry, Research Center for Experimental Medicine (CeRMS), University of Torino, Torino, Italy Several chemokines/chemokine receptors such as CCR7, Additional prognostic markers are surface CD38 and intra- CXCR4 and CXCR5 attract chronic lymphocytic leukemia cellular ZAP-70 whose expression in leukemic cells correlates (CLL) cells to specific microenvironments. Here we have with unfavorable clinical outcome.2,4,5 Finally, different chro- investigated whether the CX3CR1/CX3CL1 axis is involved in the interaction of CLL with their microenvironment.
    [Show full text]