DOCSLIB.ORG

Aging T Cell Chemokine Receptor Expression In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Aging T Cell Chemokine Receptor Expression In The Journal of Immunology T Cell Chemokine Receptor Expression in Aging1 Ruran Mo,* Jun Chen,* Yin Han,* Cecelia Bueno-Cannizares,* David E. Misek,† Pascal A. Lescure,† Samir Hanash,† and Raymond L. Yung2* Changes in chemokine receptor expression are important in determining T cell migration and the subsequent immune response. To better understand the contribution of the chemokine system in immune senescence we determined the effect of aging on CD4؉ T cell chemokine receptor function using microarray, RNase protection assays, Western blot, and in vitro chemokine transmi- ,gration assays. Freshly isolated CD4؉ cells from aged (20–22 mo) mice were found to express a higher level of CCR1, 2, 4, 5, 6 and 8 and CXCR2–5, and a lower level of CCR7 and 9 than those from young (3–4 mo) animals. Caloric restriction partially or completely restored the aging effects on CCR1, 7, and 8 and CXCR2, 4, and 5. The aging-associated differences in chemokine receptor expression cannot be adequately explained by the age-associated shift in the naive/memory or Th1/Th2 profile. CD4؉ cells from aged animals have increased chemotactic response to stromal cell-derived factor-1 and macrophage-inflammatory protein- 1␣, suggesting that the observed chemokine receptor changes have important functional consequences. We propose that the aging-associated changes in T cell chemokine receptor expression may contribute to the different clinical outcome in T cell chemokine receptor-dependent diseases in the elderly. The Journal of Immunology, 2003, 170: 895–904. he precise mechanisms linking the aging immune system (6–8). T cell-tropic HIV-1 isolates (X4 strains) preferentially use to diseases in the elderly are poorly understood. Studies in CXCR4 as a coreceptor for lymphocyte entry (9), whereas CCR5 T humans and animal models have demonstrated aging-as- acts as a cofactor by macrophage-tropic (R5 strains) and dual- sociated defects in selected inductive and effector T cell functions, tropic strains of HIV-1 (10–13). Recent data suggest that their most notably, decreased reactivity to Ag, impaired delayed hyper- level of expression is an important determinant of HIV-1 infectiv- sensitivity response to recall Ag, and diminished T cell-dependent ity and replication (14–16). In addition, the chemokine system is Ab response after vaccination (1–3). However, the notion that the extremely complex with significant redundancy. For example, aging-associated “decline” in immune response is the cause of di- some M-tropic strains of HIV can use CCR2 or 3 as coreceptor minished protective immunity and poor clinical outcome in the instead of CCR5. Ligands of chemokine receptors also affect their elderly is not supported by available evidence. With the aging function. CCR5-using chemokines (RANTES, macrophage-in- population there is an urgent need to better understand the changes flammatory protein (MIP)3-1␣, MIP-1␤) can block M-tropic HIV in immunity that occur with aging. Defining these changes will strains, whereas the CXCR4 ligand stromal cell-derived factor help to explain the susceptibility of the elderly to aging-related (SDF)-1 blocks T-tropic strains by down-regulating the receptor by guest on October 1, 2021. Copyright 2003 Pageant Media Ltd. diseases and to better predict the therapeutic response of older (14). The clinical courses of these T cell chemokine-dependent adults to biologics and immunization. diseases are different in the elderly compared with younger indi- Chemokines are a superfamily of small proteins important in viduals (17, 18). In the case of HIV-1 infection, it has been shown determining normal and pathological immune and inflammatory that older patients have a shorter observed AIDS-free interval and responses. They are classified according to the cysteine motif into shorter survival, along with more HIV and non-HIV related co- C, CC, CXC, and CX3C chemokines. In addition, at least 19 che- morbidity. This raises the possibility that aging-associated alter- mokine receptors have been identified (4, 5). These G protein- ation in chemokine response may play an important pathogenic coupled cell surface receptors possess a 7-transmembrane domain role in these diseases in older adults. http://classic.jimmunol.org and are widely distributed in lymphoid and nonlymphoid cells. Lymphocyte chemokine receptor expression has been shown to be Materials and Methods important in a number of disease processes. For example, CCR4, Mice CCR5, CXCR3, and CX3CR1 are critical in the recruitment and Young (3–4 mo), middle-aged (12–14 mo), and old (20–22 mo) C57BL/6 retention of leukocytes in the joints of rheumatoid arthritis patients and DBA/2, and caloric-restricted C57BL/6 old (20–21 mo) mice were obtained from the National Institute on Aging aged rodent colonies through Harlan Sprague Dawley (Indianapolis, IN).4 The caloric restriction proto- Downloaded from *Divisions of Geriatric Medicine and Rheumatology, Department of Internal Medi- col can be obtained through the National Institute on Aging (http://www. cine, and †Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109 nia.nih.gov). Briefly, caloric restriction is initiated at 14 wk of age at 10% Received for publication August 26, 2002. Accepted for publication November restriction, increased to 25% restriction at 15 wk, and to 40% restriction at 5, 2002. 16 wk where it is maintained throughout the life of the animal. With the exception of the caloric-restricted mice that were sacrificed within 24 h of The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 3 Abbreviations used in this paper: MIP, macrophage-inflammatory protein; SDF, 1 This work was supported by Public Health Service Grants 1K08AR01977-01A1, stromal cell-derived factor; RPA, RNase protection assay. 1RO1 AI42753, 1RO1 HL61577, American Federation for Aging Research (Paul 4 Strain contamination of the C57BL/6 breeding colony in the National Institute on Beeson Physician Faculty Scholar Award), the University of Michigan Nathan Shock Aging contract aging mouse colony at Harlan Sprague Dawley with 129 or FVB was Center (AG13282), and the Geriatrics Research, Education, and Clinical Center of the recently discovered, affecting some aging mice with C57BL/6 background. The ev- Ann Arbor Veterans Affair Medical Center. idence indicates that the strain contamination first hit the aging colony with the spring 2 Address correspondence and reprint requests to Dr. Raymond L. Yung, Room 5312 or summer 2000 dates of birth. The mice used in this manuscript were born before the Cancer Center and Geriatrics Center Building, 1500 East Medical Center Drive, Ann estimated contamination date or were deemed to be of “low risk” by the National Arbor, MI 48109-0940. E-mail address: [email protected] Institute on Aging. Copyright © 2003 by The American Association of Immunologists, Inc. 0022-1767/03/$02.00 896 PRECISE MECHANISMS LINKING AGING IMMUNE SYSTEM TO DISEASE arrival, all mice were maintained in a pathogen-free environment provided stringent wash buffer (100 mM MES (pH 6.7), 0.1 M NaCl, 0.01% Tween by the Unit for Laboratory Animal Medicine at the University of Michigan 20) at 50°C, stained with streptavidin-PE (Molecular Probes, Eugene, OR), (Ann Arbor, MI) until they were used. washed again with 6ϫ SSPE, stained with biotinylated anti-streptavidin IgG, followed by a second staining with streptavidin-PE, and a third wash- CD4 cell isolation ing with 6ϫ SSPE. The arrays were scanned using the GeneArray scanner Careful inspection was done to exclude aged animals with cancer or lym- (Affymetrix). Data analysis was performed using GeneChip 4.0 software. ϩ ␮ ϳ phoma. CD4 T cells were then isolated by the MACS Microbeads tech- The 11k and the U74A chips contain 11,000 and 12,000 probe sets, nology (Miltenyi Biotec, Bergisch-Gladbach, Germany) according to the respectively, with each probe set representing a transcript. Each probe set manufacturer’s instructions. CD4ϩ cells were negatively selected using a typically consists of 20 perfectly complementary 25 base-long probes as combination of CD8a (Ly-2), CD11b (Mac-1), and CD19 Microbeads. Al- well as 20 mismatch probes that are identical except for an altered central ternately, CD4 cells were positively selected using CD4 (L3T4) Mi- base. We subtract the mismatch probe values from the perfect match values crobeads. Purity of the isolated cells was confirmed by flow cytometric and average the middle 50% of these differences as the expression measure analysis. Briefly, a single cell suspension was prepared by gentle teasing of for that probe set. A quantile normalization procedure was used to adjust the spleen with sterile forceps. Density gradient centrifugation was done for differences in the probe intensity distribution across different chips. We using Ficoll-Paque Plus (Amersham Pharmacia Biotech, Piscataway, NJ). then applied a monotone linear spline to each chip that mapped quantiles The live splenic mononuclear cells were then magnetically labeled with the 0.02 up to 0.98 (in increments of 0.02) exactly to the corresponding median ϩ ϩ ϩ appropriate Microbeads (10 ␮l/107 total cells) and passed through the LS quantiles for all the samples. Then, the transform log(100 max(X 100; separation column three times while placed in the magnetic field of a Midi- 0)) was applied to the data from each chip. The chemokine receptor results are then calculated as changes relative to the expression levels of unstimu- MACS separator (Miltenyi Biotec). The selected cells were then removed ϩ from the column by washing three times with 3 ml of LSϩ/VSϩ buffer lated young CD4 lymphocytes. away from the magnetic field. Purity of the isolated cells was determined by staining with the FITC-conjugated anti-CD4 RM4–5 and control IgG2a RNA protection assays (RPAs) Abs (both from BD PharMingen, San Diego, CA) and was consistently between 94–99%.
Load more

Recommended publications
  • Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3+ Regulatory T Cells
    Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3+ Regulatory T Cells This information is current as Hyung W. Lim, Jeeho Lee, Peter Hillsamer and Chang H. of September 28, 2021. Kim J Immunol 2008; 180:122-129; ; doi: 10.4049/jimmunol.180.1.122 http://www.jimmunol.org/content/180/1/122 Downloaded from References This article cites 44 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/180/1/122.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 28, 2021 *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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3؉ Regulatory T Cells1 Hyung W. Lim,* Jeeho Lee,* Peter Hillsamer,† and Chang H. Kim2* It is a question of interest whether Th17 cells express trafficking receptors unique to this Th cell lineage and migrate specifically to certain tissue sites.
    [Show full text]
  • Complete Dissertation
    VU Research Portal Chemokine Receptors CXCR3 and CXCR7 Scholten, D.J. 2012 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Scholten, D. J. (2012). Chemokine Receptors CXCR3 and CXCR7: Allosteric Ligand Binding, Biased Signaling, and Receptor Regulation. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 01. Oct. 2021 Chemokine Receptors CXCR3 and CXCR7: Allosteric Ligand Binding, Biased Signaling, and Receptor Regulation Danny Scholten The work described in this thesis was performed at the Leiden/Amsterdam Center for Drug Research (LACDR), Faculty of Sciences, Division of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081HV Amsterdam, The Netherlands. This research was performed in the framework of the Dutch public-private partnership Top Institute Pharma (TI Pharma) in project “The GPCR Forum (D1-105)”.
    [Show full text]
  • The Role of Selected Chemokines and Their Receptors in the Development of Gliomas
    International Journal of Molecular Sciences Review The Role of Selected Chemokines and Their Receptors in the Development of Gliomas Magdalena Groblewska 1, Ala Litman-Zawadzka 2 and Barbara Mroczko 1,2,* 1 Department of Biochemical Diagnostics, University Hospital in Białystok, 15-269 Białystok, Poland; [email protected] 2 Department of Neurodegeneration Diagnostics, Medical University of Białystok, 15-269 Białystok, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-85-831-8785 Received: 29 April 2020; Accepted: 22 May 2020; Published: 24 May 2020 Abstract: Among heterogeneous primary tumors of the central nervous system (CNS), gliomas are the most frequent type, with glioblastoma multiforme (GBM) characterized with the worst prognosis. In their development, certain chemokine/receptor axes play important roles and promote proliferation, survival, metastasis, and neoangiogenesis. However, little is known about the significance of atypical receptors for chemokines (ACKRs) in these tumors. The objective of the study was to present the role of chemokines and their conventional and atypical receptors in CNS tumors. Therefore, we performed a thorough search for literature concerning our investigation via the PubMed database. We describe biological functions of chemokines/chemokine receptors from various groups and their significance in carcinogenesis, cancer-related inflammation, neo-angiogenesis, tumor growth, and metastasis. Furthermore, we discuss the role of chemokines in glioma development, with particular regard to their function in the transition from low-grade to high-grade tumors and angiogenic switch. We also depict various chemokine/receptor axes, such as CXCL8-CXCR1/2, CXCL12-CXCR4, CXCL16-CXCR6, CX3CL1-CX3CR1, CCL2-CCR2, and CCL5-CCR5 of special importance in gliomas, as well as atypical chemokine receptors ACKR1-4, CCRL2, and PITPMN3.
    [Show full text]
  • CXCR6 Within T-Helper (Th) and T-Cytotoxic
    European Journal of Endocrinology (2005) 152 635–643 ISSN 0804-4643 EXPERIMENTAL STUDY CXCR6 within T-helper (Th) and T-cytotoxic (Tc) type 1 lymphocytes in Graves’ disease (GD) G Aust, M Kamprad1, P Lamesch2 and E Schmu¨cking Institute of Anatomy, 1Department of Clinical Immunology and Transfusion Medicine and 2Department of Surgery, University of Leipzig, Phillipp-Rosenthal-Str. 55, Leipzig, 04103, Germany (Correspondence should be addressed to G Aust; Email: [email protected]) Abstract Objective: In Graves’ disease (GD), stimulating anti-TSH receptor antibodies are responsible for hyperthyroidism. T-helper 2 (Th2) cells were expected to be involved in the underlying immune mech- anism, although this is still controversial. The aim of this study was to examine the expression of CXCR6, a chemokine receptor that marks functionally specialized T-cells within the Th1 and T-cyto- toxic 1 (Tc1) cell pool, to gain new insights into the running immune processes. Methods: CXCR6 expression was examined on peripheral blood lymphocytes (PBLs) and thyroid- derived lymphocytes (TLs) of GD patients in flow cytometry. CXCR6 cDNA was quantified in thyroid tissues affected by GD (n ¼ 16), Hashimoto’s thyroiditis (HT; n ¼ 2) and thyroid autonomy (TA; n ¼ 11) using real-time reverse transcriptase PCR. Results: The percentages of peripheral CXCR6þ PBLs did not differ between GD and normal subjects. CXCR6 was expressed by small subsets of circulating T-cells and natural killer (NK) cells. CXCR6þ cells were enriched in thyroid-derived T-cells compared with peripheral CD4þ and CD8þ T-cells in GD. The increase was evident within the Th1 (CD4þ interferon-gþ (IFN-gþ)) and Tc1 (CD8þIFN- gþ) subpopulation and CD8þ granzyme Aþ T-cells (cytotoxic effector type).
    [Show full text]
  • Structural Determinants of MIF Functions in CXCR2-Mediated Inflammatory and Atherogenic Leukocyte Recruitment
    Structural determinants of MIF functions in CXCR2-mediated inflammatory and atherogenic leukocyte recruitment Christian Weber*†‡, Sandra Kraemer*§, Maik Drechsler†, Hongqi Lue§, Rory R. Koenen†, Aphrodite Kapurniotu¶, Alma Zernecke†, and Ju¨ rgen Bernhagen‡§ †Institute for Molecular Cardiovascular Research (IMCAR); and §Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, 52056 Aachen, Germany; and ¶Laboratory of Peptide Biochemistry, Center of Integrated Protein Science Munchen,¨ Technische Universität, D-85350 Munich, Germany Edited by Charles A. Dinarello, University of Colorado Health Sciences Center, Denver, CO, and accepted by the Editorial Board August 15, 2008 (received for review April 25, 2008) We have recently identified the archaic cytokine macrophage ing to CCR5 (i.e., HisRS) and CCR3 (i.e., AsnRS) (9, 10), and migration inhibitory factor (MIF) as a non-canonical ligand of the fragments of TyrRS mediate pro-angiogenic activity by direct CXC chemokine receptors CXCR2 and CXCR4 in inflammatory and binding to CXCR1 through a CXCL8 (also known as interleu- atherogenic cell recruitment. Because its affinity for CXCR2 was kin-8; IL-8)-like N-terminal motif consisting of residues Glu, particularly high, we hypothesized that MIF may feature structural Leu, and Arg (ELR) (11). motives shared by canonical CXCR2 ligands, namely the conserved Macrophage migration inhibitory factor (MIF) is a long- N-terminal Glu-Leu-Arg (ELR) motif. Sequence alignment and struc- known T cell cytokine discovered more than four decades ago tural modeling indeed revealed a pseudo-(E)LR motif (Asp-44-X- that more recently has been recognized to be a key mediator of Arg-11) constituted by non-adjacent residues in neighboring loops innate immunity and pleiotropic inflammatory cytokine.
    [Show full text]
  • Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3+ Regulatory T Cells
    Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3+ Regulatory T Cells This information is current as Hyung W. Lim, Jeeho Lee, Peter Hillsamer and Chang H. of September 28, 2021. Kim J Immunol 2008; 180:122-129; ; doi: 10.4049/jimmunol.180.1.122 http://www.jimmunol.org/content/180/1/122 Downloaded from References This article cites 44 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/180/1/122.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 28, 2021 *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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3؉ Regulatory T Cells1 Hyung W. Lim,* Jeeho Lee,* Peter Hillsamer,† and Chang H. Kim2* It is a question of interest whether Th17 cells express trafficking receptors unique to this Th cell lineage and migrate specifically to certain tissue sites.
    [Show full text]
  • The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature
    International Journal of Molecular Sciences Review The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature Jan Korbecki 1 , Klaudyna Kojder 2, Patrycja Kapczuk 1, Patrycja Kupnicka 1 , Barbara Gawro ´nska-Szklarz 3 , Izabela Gutowska 4 , Dariusz Chlubek 1 and Irena Baranowska-Bosiacka 1,* 1 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] (J.K.); [email protected] (P.K.); [email protected] (P.K.); [email protected] (D.C.) 2 Department of Anaesthesiology and Intensive Care, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-281 Szczecin, Poland; [email protected] 3 Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] 4 Department of Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wlkp. 72 Av., 70-111 Szczecin, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-914661515 Abstract: Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influ- ence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 Citation: Korbecki, J.; Kojder, K.; Kapczuk, P.; Kupnicka, P.; (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors— Gawro´nska-Szklarz,B.; Gutowska, I.; CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8.
    [Show full text]
  • CXCR2 Related Chemokine Receptors, CXCR1 and Regulation
    Actin Filaments Are Involved in the Regulation of Trafficking of Two Closely Related Chemokine Receptors, CXCR1 and CXCR2 This information is current as of September 23, 2021. Alon Zaslaver, Rotem Feniger-Barish and Adit Ben-Baruch J Immunol 2001; 166:1272-1284; ; doi: 10.4049/jimmunol.166.2.1272 http://www.jimmunol.org/content/166/2/1272 Downloaded from References This article cites 61 articles, 32 of which you can access for free at: http://www.jimmunol.org/content/166/2/1272.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 23, 2021 *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 © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Actin Filaments Are Involved in the Regulation of Trafficking of Two Closely Related Chemokine Receptors, CXCR1 and CXCR2 Alon Zaslaver, Rotem Feniger-Barish, and Adit Ben-Baruch The ligand-induced internalization and recycling of chemokine receptors play a significant role in their regulation.
    [Show full text]
  • CXCR6 Deficiency Impairs Cancer Vaccine Efficacy and CD8+ Resident Memory T-­Cell Recruitment in Head and Neck and Lung Tumors
    Open access Original research J Immunother Cancer: first published as 10.1136/jitc-2020-001948 on 10 March 2021. Downloaded from CXCR6 deficiency impairs cancer vaccine efficacy and CD8+ resident memory T- cell recruitment in head and neck and lung tumors Soumaya Karaki,1,2 Charlotte Blanc,1,2 Thi Tran,1,2 Isabelle Galy- Fauroux,1,2 Alice Mougel,1,2 Estelle Dransart,3 Marie Anson,1,2 Corinne Tanchot,1,2 Lea Paolini,1,2 Nadege Gruel,4,5 Laure Gibault,6 Francoise Lepimpec- Barhes,7 Elizabeth Fabre,8 Nadine Benhamouda,9 Cecile Badoual,6 Diane Damotte,10 11 12,13 14 Emmanuel Donnadieu , Sebastian Kobold, Fathia Mami- Chouaib, 15 3 1,2,9 Rachel Golub, Ludger Johannes, Eric Tartour To cite: Karaki S, Blanc C, ABSTRACT explains why the intranasal route of vaccination is the Tran T, et al. CXCR6 deficiency most appropriate strategy for inducing these cells in the Background Resident memory T lymphocytes (TRM) impairs cancer vaccine efficacy are located in tissues and play an important role in head and neck and pulmonary mucosa, which remains a and CD8+ resident memory immunosurveillance against tumors. The presence of T major objective to overcome resistance to anti- PD-1/PD- T- cell recruitment in head and RM prior to treatment or their induction is associated to the L1, especially in cold tumors. neck and lung tumors. Journal for ImmunoTherapy of Cancer response to anti- Programmed cell death protein 1 (PD- 2021;9:e001948. doi:10.1136/ 1)/Programmed death- ligand 1 (PD- L1) immunotherapy jitc-2020-001948 and the efficacy of cancer vaccines.
    [Show full text]
  • Gene Expression Profiles in the Rat Streptococcal Cell Wall-Induced
    Available online http://arthritis-research.com/content/7/1/R101 ResearchVol 7 No 1 article Open Access Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis Inmaculada Rioja1, Chris L Clayton2, Simon J Graham2, Paul F Life1 and Marion C Dickson1 1Rheumatoid Arthritis Disease Biology Department, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK 2Transcriptome Analysis Department, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK Corresponding author: Inmaculada Rioja, [email protected] Received: 3 Jul 2004 Revisions requested: 16 Sep 2004 Revisions received: 4 Oct 2004 Accepted: 9 Oct 2004 Published: 19 Nov 2004 Arthritis Res Ther 2005, 7:R101-R117 (DOI 10.1186/ar1458)http://arthritis-research.com/content/7/1/R101 © 2004 Rioja et al., licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is cited. Abstract Experimental arthritis models are considered valuable tools for P < 0.01), showing specific levels and patterns of gene delineating mechanisms of inflammation and autoimmune expression. The genes exhibiting the highest fold increase in phenomena. Use of microarray-based methods represents a expression on days -13.8, -13, or 3 were involved in chemotaxis, new and challenging approach that allows molecular dissection inflammatory response, cell adhesion and extracellular matrix of complex autoimmune diseases such as arthritis. In order to remodelling. Transcriptome analysis identified 10 upregulated characterize the temporal gene expression profile in joints from genes (Delta > 5), which have not previously been associated the reactivation model of streptococcal cell wall (SCW)-induced with arthritis pathology and are located in genomic regions arthritis in Lewis (LEW/N) rats, total RNA was extracted from associated with autoimmune disease.
    [Show full text]
  • Role of Chemokines in Hepatocellular Carcinoma (Review)
    ONCOLOGY REPORTS 45: 809-823, 2021 Role of chemokines in hepatocellular carcinoma (Review) DONGDONG XUE1*, YA ZHENG2*, JUNYE WEN1, JINGZHAO HAN1, HONGFANG TUO1, YIFAN LIU1 and YANHUI PENG1 1Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051; 2Medical Center Laboratory, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, P.R. China Received September 5, 2020; Accepted December 4, 2020 DOI: 10.3892/or.2020.7906 Abstract. Hepatocellular carcinoma (HCC) is a prevalent 1. Introduction malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges Hepatocellular carcinoma (HCC) is the sixth most common for the treatment of HCC is the prevention or management type of cancer worldwide and the third leading cause of of recurrence and metastasis of HCC. It has been found that cancer-associated death (1). Most patients cannot undergo chemokines and their receptors serve a pivotal role in HCC radical surgery due to the presence of intrahepatic or distant progression. In the present review, the literature on the multi- organ metastases, and at present, the primary treatment methods factorial roles of exosomes in HCC from PubMed, Cochrane for HCC include surgery, local ablation therapy and radiation library and Embase were obtained, with a specific focus on intervention (2). These methods allow for effective treatment the functions and mechanisms of chemokines in HCC. To and management of patients with HCC during the early stages, date, >50 chemokines have been found, which can be divided with 5-year survival rates as high as 70% (3). Despite the into four families: CXC, CX3C, CC and XC, according to the continuous development of traditional treatment methods, the different positions of the conserved N-terminal cysteine resi- issue of recurrence and metastasis of HCC, causing adverse dues.
    [Show full text]
  • Identification of an Arg-Leu-Arg Tripeptide That Contributes to The
    www.nature.com/scientificreports OPEN Identifcation of an Arg-Leu-Arg tripeptide that contributes to the binding interface between the Received: 3 October 2017 Accepted: 15 March 2018 cytokine MIF and the chemokine Published: xx xx xxxx receptor CXCR4 Michael Lacy1, Christos Kontos2, Markus Brandhofer1, Kathleen Hille2, Sabine Gröning3, Dzmitry Sinitski1, Priscila Bourilhon1, Eric Rosenberg4, Christine Krammer1, Tharshika Thavayogarajah1, Georgios Pantouris4, Maria Bakou2, Christian Weber5,6,7, Elias Lolis4, Jürgen Bernhagen1,6,8 & Aphrodite Kapurniotu2 MIF is a chemokine-like cytokine that plays a role in the pathogenesis of infammatory and cardiovascular disorders. It binds to the chemokine-receptors CXCR2/CXCR4 to trigger atherogenic leukocyte migration albeit lacking canonical chemokine structures. We recently characterized an N-like- loop and the Pro-2-residue of MIF as critical molecular determinants of the CXCR4/MIF binding-site and identifed allosteric agonism as a mechanism that distinguishes CXCR4-binding to MIF from that to the cognate ligand CXCL12. By using peptide spot-array technology, site-directed mutagenesis, structure- activity-relationships, and molecular docking, we identifed the Arg-Leu-Arg (RLR) sequence-region 87–89 that – in three-dimensional space – ‘extends’ the N-like-loop to control site-1-binding to CXCR4. Contrary to wildtype MIF, mutant R87A-L88A-R89A-MIF fails to bind to the N-terminal of CXCR4 and the contribution of RLR to the MIF/CXCR4-interaction is underpinned by an ablation of MIF/CXCR4- specifc signaling and reduction in CXCR4-dependent chemotactic leukocyte migration of the RLR- mutant of MIF. Alanine-scanning, functional competition by RLR-containing peptides, and molecular docking indicate that the RLR residues directly participate in contacts between MIF and CXCR4 and highlight the importance of charge-interactions at this interface.
    [Show full text]