DOCSLIB.ORG

Expressing a Chemokine Receptor, XCR1 Critical Roles of a Dendritic

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Expressing a Chemokine Receptor, XCR1 Critical Roles of a Dendritic Critical Roles of a Dendritic Cell Subset Expressing a Chemokine Receptor, XCR1 Chihiro Yamazaki, Masanaka Sugiyama, Tomokazu Ohta, Hiroaki Hemmi, Eri Hamada, Izumi Sasaki, Yuri Fukuda, This information is current as Takahiro Yano, Mikako Nobuoka, Takeshi Hirashima, of September 25, 2021. Akihiko Iizuka, Katsuaki Sato, Takashi Tanaka, Katsuaki Hoshino and Tsuneyasu Kaisho J Immunol 2013; 190:6071-6082; Prepublished online 13 May 2013; Downloaded from doi: 10.4049/jimmunol.1202798 http://www.jimmunol.org/content/190/12/6071 References This article cites 61 articles, 30 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/190/12/6071.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 September 25, 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 © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Critical Roles of a Dendritic Cell Subset Expressing a Chemokine Receptor, XCR1 Chihiro Yamazaki,*,†,1 Masanaka Sugiyama,*,‡,x,{,1 Tomokazu Ohta,x,{ Hiroaki Hemmi,*,{ Eri Hamada,* Izumi Sasaki,*,{ Yuri Fukuda,*,{ Takahiro Yano,* Mikako Nobuoka,* Takeshi Hirashima,* Akihiko Iizuka,* Katsuaki Sato,‖ Takashi Tanaka,‡ Katsuaki Hoshino,*,{,# and Tsuneyasu Kaisho*,{ Dendritic cells (DCs) consist of various subsets that play crucial roles in linking innate and adaptive immunity. In the murine spleen, CD8a+ DCs exhibit a propensity to ingest dying/dead cells, produce proinflammatory cytokines, and cross-present Ags to generate CD8+ T cell responses. To track and ablate CD8a+ DCs in vivo, we generated XCR1-venus and XCR1-DTRvenus mice, in which genes for a fluorescent protein, venus, and a fusion protein consisting of diphtheria toxin receptor and venus were knocked into the gene Downloaded from locus of a chemokine receptor, XCR1, which is highly expressed in CD8a+ DCs. In both mice, venus+ cells were detected in the majority of CD8a+ DCs, but they were not detected in any other cells, including splenic macrophages. Venus+CD8a+ DCs were superior to venus2CD8a+ DCs with regard to their cytokine-producing ability in response to TLR stimuli. In other tissues, venus+ cells were found primarily in lymph node (LN)-resident CD8a+, LN migratory and peripheral CD103+ DCs, which are closely related to splenic CD8a+ DCs, although some thymic CD8a2CD11b2 and LN CD1032CD11b2 DCs were also venus+. In response to dsRNAs, + + diphtheria toxin–treated XCR1-DTR mice showed impaired CD8 T cell responses, with retained cytokine and augmented CD4 T cell http://www.jimmunol.org/ responses. Furthermore, Listeria monocytogenes infection and anti–L. monocytogenes CD8+ T cell responses were defective in diph- theria toxin–treated XCR1-DTRvenus mice. Thus, XCR1-expressing DCs were required for dsRNA- or bacteria-induced CD8+ T cell responses. XCR1-venus and XCR1-DTRvenus mice should be useful for elucidating the functions and behavior of XCR1-expressing DCs, including CD8a+ and CD103+ DCs, in lymphoid and peripheral tissues. The Journal of Immunology, 2013, 190: 6071–6082. endritic cells (DCs) are specialized APCs that play crucial pathogenesis of immune disorders have been clarified by analyzing roles in linking innate and adaptive immunity (1). Critical mutant mice in which diphtheria toxin receptor (DTR) and diph- in vivo roles for DCs in various immune responses or the theria toxin (DT) A subunit are expressed under the control of the D by guest on September 25, 2021 CD11c promoter (2–6). Those mice also enabled us to clarify ho- *Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunol- meostatic roles for DCs in lymphocyte homing to lymph nodes ogy, Yokohama, Kanagawa 230-0045, Japan; †Department of Immunology, Graduate (LNs) or preventing autoimmunity (5–7). However, because DCs School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, are heterogeneous and can be divided into several subsets according Okayama, Okayama 700-8558, Japan; ‡Research Unit for Inflammatory Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230- to function and expression patterns of cell surface molecules, a DC x 0045, Japan; Laboratory of Immune Regulation, Department of Microbiology and subset–specific ablation system should be generated. Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565- 0871, Japan; {Laboratory for Immune Regulation, World Premier International Re- Under steady-state conditions, murine splenic DCs consist of 2 search Center Initiative, Immunology Frontier Research Center, Osaka University, B220+CD11cdull plasmacytoid DCs (pDCs) and B220 CD11c+ Suita, Osaka 565-0871, Japan; ‖Laboratory for Dendritic Cell Immunobiology, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; DCs. In the spleen, all DCs are resident DCs derived from blood 2 + + and #Department of Immunology, Faculty of Medicine, Kagawa University, Kita-gun, precursors, and B220 CD11c DCs can be divided into CD8a Kagawa 761-0793, Japan CD11b2 and CD8a2CD11b+ DCs. In lymphoid tissues, DCs con- 1 C.Y. and M.S. contributed equally to this work. sist of resident and migratory DCs, which can be defined as MHC Received for publication October 9, 2012. Accepted for publication April 4, 2013. class II (MHC-II)intCD11c+ and MHC-IIhighCD11c+ DCs, re- This work was supported by the Kishimoto Foundation, a Grant-in-Aid for Scientific spectively (8, reviewed in Ref. 9). As in the spleen, resident DCs Research (B, C), a Grant-in-Aid for Challenging Exploratory Research, a Grant-in-Aid for + 2 2 + Scientific Research on Priority Areas, a Grant-in-Aid for Scientific Research on Innova- consist mainly of CD8a CD11b and CD8a CD11b cells. Mi- tive Areas, the Uehara Memorial Foundation, and a Grant-in-Aid for Young Scientists. gratory DCs are derived from peripheral tissues, such as skin or C.Y., M.S., and I.S. were supported by a RIKEN Junior Research Associate grant. lamina propria, and can be divided into several subsets depending Address correspondence and reprint requests to Dr. Tsuneyasu Kaisho, Laboratory of on the expression patterns of CD103 and CD11b. Immune Regulation, World Premier International Research Center Initiative, Immunology + Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Among these DC subsets, resident CD8a DCs and migratory Japan. E-mail address: [email protected] CD103+ DCs are characterized by their ability to take up apoptotic Abbreviations used in this article: DC, dendritic cell; DT, diphtheria toxin; DTR, cells and to cross-present soluble and cell-associated Ags for diphtheria toxin receptor; EGFP, enhanced GFP; ES, embryonic stem; Flt3L, Flt3 + ligand; LC, Langerhans cell; L.m.-OVA, Listeria monocytogenes expressing OVA; generating CD8 cytotoxic T cells (10–12, reviewed in Ref. 13). LN, lymph node; MF, macrophage; MHC-II, MHC class II; mLN, mesenteric lymph This cross-presenting activity is important for establishing anti- node; Mo-DC, monocyte-derived dendritic cell; mOVA-Tg, C57BL/6-Tg(CAG-OVA) viral or antitumor immunity. Cross-presentation can be facilitated 916Jen/J; MZMMF, marginal zone metallophilic macrophage; pDC, plasmacytoid dendritic cell; poly(I:C), polyinosinic-polycytidylic acid; SDLN, skin-draining lymph by targeting Ags to several C-type lectins, such as DEC-205 node; Tip-DC, TNF-a/inducible NO synthase–producing dendritic cell; WT, wild-type; (CD205), Clec9a, and Langerin (CD207), expressed on these XCR1, XC chemokine receptor 1. DC subsets (14–16). Splenic CD8a+ DCs also show a propensity Copyright Ó 2013 by The American Association of Immunologists, Inc. 0022-1767/13/$16.00 to produce proinflammatory cytokines in response to a LPS sen- www.jimmunol.org/cgi/doi/10.4049/jimmunol.1202798 6072 IN VIVO FUNCTIONS OF XCR1-EXPRESSING CELLS sor, TLR4, and nucleic acid sensors, TLR3 and TLR9. It is im- Germline-transmitting chimeras were generated by injection of targeted ES portant to clarify the in vivo roles of this DC subset. clones to blastocysts from BALB/c mice and bred with C57BL/6J mice. Obtained Xcr1+/venus and Xcr1+/DTRvenus mice were backcrossed with Several mutant mice lacking this DC subset have been estab- C57BL/6J mice for an additional two to six or two to four generations, lished and analyzed. Although the mutant mice lacking a tran- respectively. C57BL/6J or Xcr1+/+ littermates were used as wild-type (WT) scription factor, IRF-8, show ablation of both CD8a+ DCs and mice. pDCs, spontaneous mutant mice (BXH2 mice) carrying a point Mice mutation on the Irf8 gene lack only CD8a+ DCs (17, 18). CD8a+ C57BL/6J mice were purchased from CLEA Japan. b2m-deficient DCs are also ablated in the mutant mice lacking a basic leucine tm1Unc zipper transcription factor, ATF-like 3 (BATF3) (19). Both tran- (B6.129P2-B2m /J)
Load more

Recommended publications
  • Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species
    International Journal of Molecular Sciences Review Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species Mohammed Yusuf Zanna 1 , Abd Rahaman Yasmin 1,2,* , Abdul Rahman Omar 2,3 , Siti Suri Arshad 3, Abdul Razak Mariatulqabtiah 2,4 , Saulol Hamid Nur-Fazila 3 and Md Isa Nur Mahiza 3 1 Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia; [email protected] 2 Laboratory of Vaccines and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia; [email protected] (A.R.O.); [email protected] (A.R.M.) 3 Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia; [email protected] (S.S.A.); [email protected] (S.H.N.-F.); [email protected] (M.I.N.M.) 4 Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia * Correspondence: [email protected]; Tel.: +603-8609-3473 or +601-7353-7341 Abstract: Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout the body. They are the most effi- cient, potent, and professional antigen-presenting cells (APCs) of the immune system, inducing and dispersing a primary immune response by the activation of naïve T-cells, and playing an important role in the induction and maintenance of immune tolerance under homeostatic conditions. Thus, this Citation: Zanna, M.Y.; Yasmin, A.R.; review has elucidated the general aspects of DCs as well as the current dynamic perspectives and Omar, A.R.; Arshad, S.S.; distribution of DCs in humans and in various species of animals that includes mouse, rat, birds, dog, Mariatulqabtiah, A.R.; Nur-Fazila, cat, horse, cattle, sheep, pig, and non-human primates.
    [Show full text]
  • Expression and Function of the Chemokine Receptor XCR1 on Murine CD8+ DC
    Dissertation Expression and function of the chemokine receptor XCR1 on murine CD8+ DC zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) im Fach Biologie eingereicht an der Mathematisch-Naturwissenschaftlichen Fakultät I der Humboldt-Universität zu Berlin von Master Biochemiker Ahmed Mora geboren am 27.12.1978 in Lyon Präsident der Humboldt-Universität zu Berlin Prof. Dr. Dr. h.c. Christoph Markschies Dekan der Mathematisch-Naturwissenschaftlichen Fakultät I Prof. Dr. Lutz-Helmut Schön Gutachter: 1. Prof. Dr. Peter-Michael Kloetzel 2. Prof. Dr. Richard Kroczek 3. Dr. Michal Or-Guil Tag der mündlichen Prüfung:16-03-2010 Summary The G protein-coupled receptor XCR1 has been described as the sole receptor for the chemokine ATAC. As contradictory data were published on the expression pattern of XCR1, its role in the immune system has not yet been defined. In this work, expression of XCR1 was characterized in B6.XCR1-lacZ+/+ reporter mice which express β-galactosidase under the control of the XCR1 promoter. In tissue sections, strong expression of XCR1 was only detected in lymphoid organs like spleen, lymph nodes and thymus. In the spleen, XCR1+ cells were mainly found in the marginal zones, but also in the red pulp and the T cell zones. Flow cytometric analysis demonstrated exclusive expression of XCR1 on DC, mainly on the CD8+ DC subset, but also on a minority of CD4− CD8− DC. In vivo, these XCR1+ cells migrated in response to chemotactic or inflammatory stimuli: application of either an ATAC-expressing cell line or LPS induced within 3 - 9 h the translocation of XCR1+ cells to the T cell area of the spleen.
    [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]
  • CX3CR1 Cd8α Dendritic Cells Are a Steady-State Population Related to Plasmacytoid Dendritic Cells
    + + CX3CR1 CD8α dendritic cells are a steady-state population related to plasmacytoid dendritic cells Liat Bar-Ona,1, Tal Birnberga,1, Kanako L. Lewisb, Brian T. Edelsonc, Dunja Bruderd, Kai Hildnerc,e,2, Jan Buerf, Kenneth M. Murphyc,e, Boris Reizisb, and Steffen Junga,3 aDepartment of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel; bDepartment of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032; cDepartment of Pathology and Immunology and eHoward Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110; dImmune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany; and fDepartment of Medical Microbiology, University Hospital Essen, Essen 45147, Germany Edited by Ralph M. Steinman, The Rockefeller University, New York, NY, and approved July 13, 2010 (received for review February 19, 2010) Lymphoid organs are characterized by a complex network of precDC (3, 22, 23), develop locally in the bone marrow, and are phenotypically distinct dendritic cells (DC) with potentially unique relatively long lived in the periphery (24, 25). PDC display a roles in pathogen recognition and immunostimulation. Classical number of lymphocytic features, including the presence of Ig D–J DC (cDC) include two major subsets distinguished in the mouse by rearrangements as the result of RAG protein expression during the expression of CD8α. Here we describe a subset of CD8α+ DC in their development (26). The generation of PDC is controlled specifically by the transcriptional regulator E2-2 (27). lymphoid organs of naïve mice characterized by expression of the + + + Here we report the characterization of a murine CD8α DC CX3CR1 chemokine receptor.
    [Show full text]
  • Cx3cr1 Mediates the Development of Monocyte-Derived Dendritic Cells During Hepatic Inflammation
    CX3CR1 MEDIATES THE DEVELOPMENT OF MONOCYTE-DERIVED DENDRITIC CELLS DURING HEPATIC INFLAMMATION. Supplementary material Supplementary Figure 1: Liver CD45+ myeloid cells were pre-gated for Ly6G negative cells for excluding granulocytes and HDCs subsequently analyzed among the cells that were CD11c+ and had high expression of MHCII. Supplementary Table 1 low/- high + Changes in gene expression between CX3CR1 and CX3CR1 CD11b myeloid hepatic dendritic cells (HDCs) from CCl4-treated mice high Genes up-regulated in CX3CR1 HDCs Gene Fold changes P value Full name App 4,01702 5,89E-05 amyloid beta (A4) precursor protein C1qa 9,75881 1,69E-22 complement component 1, q subcomponent, alpha polypeptide C1qb 9,19882 3,62E-20 complement component 1, q subcomponent, beta polypeptide Ccl12 2,51899 0,011769 chemokine (C-C motif) ligand 12 Ccl2 6,53486 6,37E-11 chemokine (C-C motif) ligand 2 Ccl3 4,99649 5,84E-07 chemokine (C-C motif) ligand 3 Ccl4 4,42552 9,62E-06 chemokine (C-C motif) ligand 4 Ccl6 3,9311 8,46E-05 chemokine (C-C motif) ligand 6 Ccl7 2,60184 0,009272 chemokine (C-C motif) ligand 7 Ccl9 4,17294 3,01E-05 chemokine (C-C motif) ligand 9 Ccr2 3,35195 0,000802 chemokine (C-C motif) receptor 2 Ccr5 3,23358 0,001222 chemokine (C-C motif) receptor 5 Cd14 6,13325 8,61E-10 CD14 antigen Cd36 2,94367 0,003243 CD36 antigen Cd44 4,89958 9,60E-07 CD44 antigen Cd81 6,49623 8,24E-11 CD81 antigen Cd9 3,06253 0,002195 CD9 antigen Cdkn1a 4,65279 3,27E-06 cyclin-dependent kinase inhibitor 1A (P21) Cebpb 6,6083 3,89E-11 CCAAT/enhancer binding protein (C/EBP),
    [Show full text]
  • Immune System the Regional Specialization of the Mucosal And
    The Role of Thymus-Expressed Chemokine and Its Receptor CCR9 on Lymphocytes in the Regional Specialization of the Mucosal Immune System This information is current as of September 25, 2021. Konstantinos A. Papadakis, John Prehn, Viera Nelson, Lorna Cheng, Scott W. Binder, Paul D. Ponath, David P. Andrew and Stephan R. Targan J Immunol 2000; 165:5069-5076; ; doi: 10.4049/jimmunol.165.9.5069 Downloaded from http://www.jimmunol.org/content/165/9/5069 References This article cites 45 articles, 22 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/165/9/5069.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 September 25, 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 © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Role of Thymus-Expressed Chemokine and Its Receptor CCR9 on Lymphocytes in the Regional Specialization of the Mucosal Immune System1 Konstantinos A. Papadakis,2* John Prehn,* Viera Nelson,† Lorna Cheng,† Scott W.
    [Show full text]
  • CCR4 Is Critically Involved in Effective Antitumor Immunity in Mice Bearing Intradermal B16 Melanoma
    Cancer Letters 378 (2016) 16–22 Contents lists available at ScienceDirect Cancer Letters journal homepage: www.elsevier.com/locate/canlet Original Articles CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma Kazuhiko Matsuo a, Tatsuki Itoh b, Atsushi Koyama a, Reira Imamura a, Shiori Kawai a, Keiji Nishiwaki c, Naoki Oiso d, Akira Kawada d, Osamu Yoshie e, Takashi Nakayama a,* a Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan b Department of Food Science and Nutrition, Kindai University Faculty of Agriculture, Nara, Japan c Division of Computational Drug Design and Discovery, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan d Department of Dermatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan e Department of Microbiology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan ARTICLE INFO ABSTRACT Article history: CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known Received 1 March 2016 to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of an- Received in revised form 23 April 2016 titumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon Accepted 25 April 2016 intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph Keywords: nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were Chemokine found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph CCR4 Melanoma nodes.
    [Show full text]
  • COMPREHENSIVE INVITED REVIEW Chemokines and Their Receptors
    COMPREHENSIVE INVITED REVIEW Chemokines and Their Receptors Are Key Players in the Orchestra That Regulates Wound Healing Manuela Martins-Green,* Melissa Petreaca, and Lei Wang Department of Cell Biology and Neuroscience, University of California, Riverside, California. Significance: Normal wound healing progresses through a series of over- lapping phases, all of which are coordinated and regulated by a variety of molecules, including chemokines. Because these regulatory molecules play roles during the various stages of healing, alterations in their presence or function can lead to dysregulation of the wound-healing process, potentially leading to the development of chronic, nonhealing wounds. Recent Advances: A discovery that chemokines participate in a variety of disease conditions has propelled the study of these proteins to a level that potentially could lead to new avenues to treat disease. Their small size, ex- posed termini, and the fact that their only modifications are two disulfide Manuela Martins-Green, PhD bonds make them excellent targets for manipulation. In addition, because they bind to G-protein-coupled receptors (GPCRs), they are highly amenable to Submitted for publication January 9, 2013. *Correspondence: Department of Cell Biology pharmacological modulation. and Neuroscience, University of California, Riv- Critical Issues: Chemokines are multifunctional, and in many situations, their erside, Biological Sciences Building, 900 Uni- functions are highly dependent on the microenvironment. Moreover, each versity Ave., Riverside, CA 92521 (email: [email protected]). specific chemokine can bind to several GPCRs to stimulate the function, and both can function as monomers, homodimers, heterodimers, and even oligo- mers. Activation of one receptor by any single chemokine can lead to desen- Abbreviations sitization of other chemokine receptors, or even other GPCRs in the same cell, and Acronyms with implications for how these proteins or their receptors could be used to Ang-2 = angiopoietin-2 manipulate function.
    [Show full text]
  • Stimulation of Oral Fibroblast Chemokine Receptors Identifies CCR3 and CCR4 As Potential Wound Healing Targets†
    ORIGINAL RESEARCH ARTICLE Stimulation of oral fibroblast chemokine receptors identifies CCR3 and CCR4 as potential wound healing targets† Jeroen Kees Buskermolen1, Sanne Roffel1, Susan Gibbs1,2,* 1 Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands 2 Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands *Corresponding author: Prof. Susan Gibbs, [email protected]; Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands Running head: Oral fibroblast chemokine-receptor function Keywords: Gingiva Chemokine Cytokine Proliferation Migration Abbreviations: ACKR atypical chemokine receptor ECM extracellular matrix ELISA enzyme-linked immunosorbent assay HGF hepatic growth factor hTERT human telomerase reverse transcriptase IL interleukin MEC mucosae-associated epithelial chemokine TIMP-1 tissue-inhibitor-of-metalloproteinase-1 †This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: [10.1002/jcp.25946] Received 16 February 2017; Revised 5 April 2017; Accepted 5 April 2017 Journal of Cellular Physiology This article is protected by copyright. All rights reserved DOI 10.1002/jcp.25946 This article is protected by copyright. All rights reserved 1 Abstract The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa.
    [Show full text]
  • Role of Chemokines in Non-Small Cell Lung Cancer: Angiogenesis and Inflammation
    Journal of Cancer 2015, Vol. 6 938 Ivyspring International Publisher Journal of Cancer 2015; 6(10): 938-952. doi: 10.7150/jca.12286 Review Role of Chemokines in Non-Small Cell Lung Cancer: Angiogenesis and Inflammation Selma Rivas-Fuentes1, Alfonso Salgado-Aguayo2, Silvana Pertuz Belloso3, Patricia Gorocica Rosete1, Noé Alvarado-Vásquez1, Guillermo Aquino-Jarquin4 1. Department of Biochemistry Research, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Mexico City, Mexico. 2. Laboratory of Research on Rheumatic Diseases, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Mexico City, Mexico. 3. Department of Comparative Biology, Faculty of Sciences, National Autonomous University of Mexico, Mexico City, Mexico. 4. Laboratory of Research on Genomics, Genetics and Bioinformatics. Tower of Haemato-oncology, Children´s Hospital of Mexico “Federico Gomez”, Mexico City, Mexico. Corresponding author: Department of Biochemistry Research, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Mexico City, Mexico. Calzada de Tlalpan 4502, Tlalpan, Ciudad de México, D.F. 14080, México. Phone +52 (55) 5487 1705; E-mail: [email protected]. © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. Received: 2015.03.30; Accepted: 2015.06.23; Published: 2015.08.07 Abstract Non-small cell lung cancer (NSCLC) is one of the most common types of aggressive cancer. The tumor tissue, which shows an active angiogenesis, is composed of neoplastic and stromal cells, and an abundant inflammatory infiltrate. Angiogenesis is important to support tumor growth, while infiltrating cells contribute to the tumor microenvironment through the secretion of growth factors, cytokines and chemokines, important molecules in the progression of the disease.
    [Show full text]
  • Chemokine and Chemokine Receptor Profiles in Metastatic Salivary Adenoid Cystic Carcinoma ASHLEY C
    ANTICANCER RESEARCH 36 : 4013-4018 (2016) Chemokine and Chemokine Receptor Profiles in Metastatic Salivary Adenoid Cystic Carcinoma ASHLEY C. MAYS, XIN FENG, JAMES D. BROWNE and CHRISTOPHER A. SULLIVAN Department of Otolaryngology, Wake Forest School of Medicine, Winston Salem, NC, U.S.A. Abstract. Aim: To characterize the chemokine pattern in distant metastasis (2-5). According to Ko et al. , 75% of metastatic salivary adenoid cystic carcinoma (SACC). patients with initial nodal involvement eventually developed Materials and Methods: Real-time polymerase chain distant metastasis. Patients with lung metastasis have a poor reaction (RT-PCR) was used to compare chemokine and prognosis (6). chemokine receptor gene expression in two SACC cell lines: The development of distant metastatic disease is the chief SACC-83 and SACC-LM (lung metastasis). Chemokines and cause for mortality (7, 8). Primary treatment is complete receptor genes were then screened and their expression surgical resection when feasible with adjuvant radiotherapy. pattern characterized in human tissue samples of non- The role of chemotherapy is debatable. Treatment of recurrent SACC and recurrent SACC with perineural metastatic ACC has been difficult to date due to lack of invasion. Results: Expression of chemokine receptors specific targets for metastatic cells (1). Though the steps that C5AR1, CCR1, CCR3, CCR6, CCR7, CCR9, CCR10, must occur in the metastatic event are well characterized, it CXCR4, CXCR6, CXCR7, CCRL1 and CCRL2 were higher remains unclear why or how ACC cells ultimately “choose” in SACC-83 compared to SACC-LM. CCRL1, CCBP2, or are ”chosen” to migrate to a specific metastatic site. A CMKLR1, XCR1 and CXCR2 and 6 chemokine genes mounting body of evidence suggests that cytokine-like (CCL13, CCL27, CXCL14, CMTM1, CMTM2, CKLF) were molecules called chemokines play a significant role in more highly expressed in tissues of patients without tumor directing the cellular traffic in metastatic melanoma, lung, recurrence/perineural invasion compared to those with breast and ACC cancers (9-15).
    [Show full text]
  • "Chemokines and Chemokine Receptors". In: Encyclopedia of Life Sciences (ELS)
    Chemokines and Advanced article Chemokine Receptors Article Contents . Introduction Manel Juan, Servei d’Immunologia, Hospital Clı´nic (CDB), Institut d’Investigacions Biome`diques . Chemokine Receptors . Chemokine Families August Pi i Sunyer, Barcelona, Catalonia, Spain . High Variability in the Chemokine Network Roger Colobran, Laboratori d’Immunobiologia per a la Recerca i Aplicacions Diagno` stiques . Role of Chemokines in Normal Immune System (LIRAD), Banc de Sang i Teixits (BST), Institut d’Investigacio´ en Cie`ncies de la Salut Germans Trias i Pujol . Role of Chemokines in Disease (IICSGTiP), Badalona, Catalonia, Spain Online posting date: 15th December 2009 Based in part on the previous version of this Encyclopedia of Life Sciences (ELS) article, Chemokines by Richard Horuk. Chemokines (CKs) are a family of small proteins secreted cells to recirculate with precision and fine coordination by a great variety of cell types. Their name (derived from around all body tissues, selecting continuously specific chemoattractant cytokines) is due to their ability to induce anatomic sites to develop each step of immune responses. directed chemotaxis in nearby responsive cells. Some CKs This efficiency in immune response is obtained in part by the coordinated synthesis and function of the small cyto- are considered pro-inflammatory and can be induced kines called chemokines (CKs) and their action on their during an immune response to promote cells of the counterparts, the chemokine receptors (CKRs); in fact, immune system to a site of infection, whereas others are CKRs define the subpopulation that will be localized in considered homeostatic and are involved in controlling each step of the immune responses. See also: Chemoattrac- the migration of cells during normal processes of tissue tion: Basic Concepts and Role in the Immune Response maintenance or development.
    [Show full text]