The Biology of Chemokines and their Receptors

Rossi, Devora; Zlotnik, Albert

doi:10.1146/annurev.immunol.18.1.217

Cited by 2,410Chemokine receptors and signalingInflammation biomarkers and pathwaysCytokine Signaling Pathways and Interactions

The Biology of Chemokines and their Receptors

Rossi, Devora, Zlotnik, Albert·2000·Annual Review of Immunology

DOI 10.1146/annurev.immunol.18.1.217

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Abstract

During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors. The chemokine field has also received considerable attention since chemokine receptors were found to act as co-receptors for HIV infection ( 1 ). In addition, chemokines, along with adhesion molecules, are crucial during inflammatory responses for a timely recruitment of specific leukocyte subpopulations to sites of tissue damage. However, chemokines and their receptors are also important in dendritic cell maturation ( 2 ), B ( 3 ), and T ( 4 ) cell development, Th1 and Th2 responses, infections, angiogenesis, and tumor growth as well as metastasis ( 5 ). Furthermore, an increase in the number of chemokine/receptor transgenic and knock-out mice has helped to define the functions of chemokines in vivo. In this review we discuss some of the chemokines’ biological effects in vivo and in vitro, described in the last few years, and the implications of these findings when considering chemokine receptors as therapeutic targets.

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Chemokine biology extends to all cell types, including most human neoplastic cells.
“Chemokines were initially defined functionally as soluble factors regulating directional migration of leukocytes during states of inflammation; however, chemokine biology extends to all cell types, including most human neoplastic cells6.”
From Inflammation and cancer (2002) · cites this paper as [6]
CXCL12 is the product of resting cells in multiple organs.
“CXCL12 is a rather unique chemokine in that it is the product of resting cells in multiple organs6”
From Inflammation and cancer (2002) · cites this paper as [6]
ELR− CXC ligands bind to CXCR3, CXCR4 and CXCR5.
“whereas ELR− CXC ligands bind to CXCR3, CXCR4 and CXCR5 (ref. 6).”
From Inflammation and cancer (2002) · cites this paper as [6]
ELR+ CXC ligands bind to CXCR2 and to a lesser degree to CXCR1.
“ELR+ CXC ligands bind to CXCR2 and to a lesser degree to CXCR1”
From Inflammation and cancer (2002) · cites this paper as [6]

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Cytokine networks in solid human tumors: regulation of angiogenesis
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Mechanism and biological significance of constitutive expression of MGSA/GRO chemokines in malignant melanoma tumor progression
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The CC Chemokine Receptor-7 Ligands 6Ckine and Macrophage Inflammatory Protein-3β Are Potent Chemoattractants for In Vitro- and In Vivo-Derived Dendritic Cells
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Cutting Edge: Identification of the Orphan Chemokine Receptor GPR-9-6 as CCR9, the Receptor for the Chemokine TECK
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Induction of interferon-γ production in Th1 CD4+ T cells: evidence for two distinct pathways for promoter activation
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Transforming Growth Factor β Production Is Inversely Correlated with Severity of Murine Malaria Infection
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HuMig: A New Human Member of the Chemokine Family of Cytokines
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Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic keratinocytes mediates angiogenesis.
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Mechanisms of tumour metastasis
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A Novel Mutant Gene Involved in T-Lymphocyte–Specific Homing Into Peripheral Lymphoid Organs on Mouse Chromosome 4
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Islet-Specific Th1, But Not Th2, Cells Secrete Multiple Chemokines and Promote Rapid Induction of Autoimmune Diabetes
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Lymphotactin is produced by NK cells and attracts both NK cells and T cells in vivo
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Identification and characterization of a novel beta chemokine containing six conserved cysteines
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Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease
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Identification of CRG-2. An interferon-inducible mRNA predicted to encode a murine monokine.
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The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer
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Role of natural killer cells and TCRγ δ T cells in acute autoimmune encephalomyelitis
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Interleukin 10 suppresses tumor growth and metastasis of human melanoma cells: potential inhibition of angiogenesis.
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Contribution of the CXC chemokines IP-10 and Mig to the antitumor effects of IL-12
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Regulation of the expression of the VEGF/VPS and its receptors: role in tumor angiogenesis
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Isolation and characterization of Exodus-2, a novel C-C chemokine with a unique 37-amino acid carboxyl-terminal extension
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HCC-1, a novel chemokine from human plasma.
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The CC chemokine antagonist Met‐RANTES inhibits eosinophil effector functions through the chemokine receptors CCR1 and CCR3
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Reduced Tumorigenicity and Augmented Leukocyte Infiltration After Monocyte Chemotactic Protein-3 ( MCP-3 ) Gene Transfer: Perivascular Accumulation of Dendritic Cells in Peritumoral Tissue and Neutrophil Recruitment Within the Tumor
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Identification of a new mouse beta-chemokine, thymus-derived chemotactic agent 4, with activity on T lymphocytes and mesangial cells
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Lymphotactin Gene-Modified Bone Marrow Dendritic Cells Act as More Potent Adjuvants for Peptide Delivery to Induce Specific Antitumor Immunity
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The CXC Receptor 2 Is Overexpressed in Psoriatic Epidermis
Kulke, R., Bornscheuer, E., Schlüter, C., Bartels, J., Röwert, J., Sticherling, M., & Christophers, E. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00074.x · Cited by 108 · see citing works
Interferon-α and interferon-γ down-regulate the production of interleukin-8 and ENA-78 in human monocytes
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Adenoviral Vectors Expressing Lymphotactin and Interleukin 2 or Lymphotactin and Interleukin 12 Synergize to Facilitate Tumor Regression in Murine Breast Cancer Models
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T-cell subsets: Chemokine receptors guide the way
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Molecular Cloning and Functional Characterization of a Novel CC Chemokine, Stimulated T Cell Chemotactic Protein (STCP-1) That Specifically Acts on Activated T Lymphocytes
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IL-2 up-regulates but IFN-gamma suppresses IL-8 expression in human monocytes.
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Early responses to infection: chemokines as mediators of inflammation
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A Candidate for Cancer Gene Therapy: MIP-lα Gene Transfer to an Adenocarcinoma Cell Line Reduced T\imorigenicity and Induced Protective Immunity in Immunocompetent Mice
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The G protein‐coupled receptor BLR1 is involved in murine B cell differentiation and is also expressed in neuronal tissues
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Inhibition of wound healing in mice by local interferon alpha/beta injection.
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Characterization of a Novel CC Chemokine, HCC-4, Whose Expression Is Increased by Interleukin-10
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Interleukin-10 Suppresses IP-10 Gene Transcription by Inhibiting the Production of Class I Interferon
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Normal immunoglobulin G protects against experimental allergic encephalomyelitis by inducing transferable T cell unresponsiveness to myelin basic protein
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Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function
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Monocyte chemoattractant protein-1 stimulates tumor necrosis and recruitment of macrophages into tumors in tumor-bearing nude mice: increased granulocyte and macrophage progenitors in murine bone marrow.
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Inflammation and cancer
Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111 · see citing works
Inflammation in Wound Repair: Molecular and Cellular Mechanisms
Eming, S. A., Krieg, T., & Davidson, J. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700701 · Cited by 2,429 · see citing works
Cancer and the chemokine network
Balkwill, F. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1388 · Cited by 2,343 · see citing works
Inflammatory and immune pathways in the pathogenesis of periodontal disease
Cekici, A., Kantarci, A., Hasturk, H., & Van Dyke, T. E. (2014) · Periodontology 2000 · doi:10.1111/prd.12002 · Cited by 1,415 · see citing works
“In addition to their cell-trafficking role, chemokines provide messages leading to other biological processes, such as angiogenesis, cell proliferation, apoptosis, tumor metastasis and host defense (48, 171, 200, 201, 267).”
Background
Molecular characterization of the tumor microenvironment in breast cancer
Allinen, M., Beroukhim, R., Cai, L., Brennan, C., Lahti-Domenici, J., Huang, H., Porter, D., Hu, M., Chin, L., Richardson, A., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.010 · Cited by 1,299 · see citing works
Chemokines in cutaneous wound healing
Gillitzer, R., & Goebeler, M. (2001) · Journal of Leukocyte Biology · doi:10.1189/jlb.69.4.513 · Cited by 943 · see citing works
The Interplay between the Glucocorticoid Receptor and Nuclear Factor-κB or Activator Protein-1: Molecular Mechanisms for Gene Repression
De Bosscher, K., Vanden Berghe, W., & Haegeman, G. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0006 · Cited by 898 · see citing works
Regulation of Dendritic Cell Migration to the Draining Lymph Node
Martín-Fontecha, A., Sebastiani, S., Höpken, U. E., Uguccioni, M., Lipp, M., Lanzavecchia, A., & Sallusto, F. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030448 · Cited by 878 · see citing works
Stromal cells in tumor microenvironment and breast cancer
Mao, Y., Keller, E. T., Garfield, D. H., Shen, K., & Wang, J. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9415-3 · Cited by 671 · see citing works
Role of chemokines in tumor growth
Raman, D., Baugher, P. J., Thu, Y. M., & Richmond, A. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.05.013 · Cited by 578 · see citing works
Stat1-dependent and -independent pathways in IFN-γ-dependent signaling
Ramana, C. V., Gil, M. P., Schreiber, R. D., & Stark, G. R. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(01)02118-4 · Cited by 555 · see citing works
Neuronal CXCL10 Directs CD8 <sup>+</sup> T-Cell Recruitment and Control of West Nile Virus Encephalitis
Klein, R. S., Lin, E., Zhang, B., Luster, A. D., Tollett, J., Samuel, M. A., Engle, M., & Diamond, M. S. (2005) · Journal of Virology · doi:10.1128/jvi.79.17.11457-11466.2005 · Cited by 424 · see citing works
Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors
Zaiss, A.-K., Liu, Q., Bowen, G. P., Wong, N. C. W., Bartlett, J. S., & Muruve, D. A. (2002) · Journal of Virology · doi:10.1128/jvi.76.9.4580-4590.2002 · Cited by 394 · see citing works
Pathophysiology of allergic inflammation
Barnes, P. J. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01020.x · Cited by 361 · see citing works
Chemokines in cancer
Vicari, A. P., & Caux, C. (2002) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(01)00033-8 · Cited by 351 · see citing works
Oxidative stress promotes myofibroblast differentiation and tumour spreading
Toullec, A., Gerald, D., Despouy, G., Bourachot, B., Cardon, M., Lefort, S., Richardson, M., Rigaill, G., Parrini, M., Lucchesi, C., et al. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000073 · Cited by 339 · see citing works
CD4+ T Cells Contribute to the Remodeling of the Microenvironment Required for Sustained Tumor Regression upon Oncogene Inactivation
Rakhra, K., Bachireddy, P., Zabuawala, T., Zeiser, R., Xu, L., Kopelman, A., Fan, A. C., Yang, Q., Braunstein, L., Crosby, E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.002 · Cited by 339 · see citing works
Interrelation of immunity and tissue repair or regeneration
Eming, S. A., Hammerschmidt, M., Krieg, T., & Roers, A. (2009) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2009.04.009 · Cited by 321 · see citing works
Role of the tumor microenvironment in tumor progression and the clinical applications (Review)
YUAN, Y., JIANG, Y.-C., SUN, C.-K., & CHEN, Q.-M. (2016) · Oncology Reports · doi:10.3892/or.2016.4660 · Cited by 320 · see citing works
Role of CCR2 in macrophage migration into the liver during acetaminophen-induced hepatotoxicity in the mouse
Dambach, D. M., Watson, L. M., Gray, K. R., Durham, S. K., & Laskin, D. L. (2002) · Hepatology · doi:10.1053/jhep.2002.33162 · Cited by 289 · see citing works
Blocking Chemokine Responsive to γ–2/Interferon (IFN)-γ Inducible Protein and Monokine Induced by IFN-γ Activity In Vivo Reduces the Pathogenetic but not the Antiviral Potential of Hepatitis B Virus–specific Cytotoxic T Lymphocytes
Kakimi, K., Lane, T. E., Wieland, S., Asensio, V. C., Campbell, I. L., Chisari, F. V., & Guidotti, L. G. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.12.1755 · Cited by 234 · see citing works
Is Endometriosis Associated with Systemic Subclinical Inflammation?
Agic, A., Xu, H., Finas, D., Banz, C., Diedrich, K., & Hornung, D. (2006) · Gynecologic and Obstetric Investigation · doi:10.1159/000093121 · Cited by 231 · see citing works
CXC chemokines located in the 4q21 region are up-regulated in breast cancer
Bieche, I., Chavey, C., Andrieu, C., Busson, M., Vacher, S., Le Corre, L., Guinebretiere, J.-M., Burlinchon, S., Lidereau, R., & Lazennec, G. (2007) · Endocrine Related Cancer · doi:10.1677/erc.1.01301 · Cited by 183 · see citing works
Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders
Stuart, M. J., Singhal, G., & Baune, B. T. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00357 · Cited by 163 · see citing works
Mechanisms of leukocyte migration across the blood-retina barrier
Crane, I. J., & Liversidge, J. (2008) · Seminars in Immunopathology · doi:10.1007/s00281-008-0106-7 · Cited by 152 · see citing works
Conceptual development of the immune system as a sixth sense
Blalock, J. E., & Smith, E. M. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.09.004 · Cited by 153 · see citing works
Chemerin regulates β-cell function in mice
Takahashi, M., Okimura, Y., Iguchi, G., Nishizawa, H., Yamamoto, M., Suda, K., Kitazawa, R., Fujimoto, W., Takahashi, K., Zolotaryov, F. N., et al. (2011) · Scientific Reports · doi:10.1038/srep00123 · Cited by 149 · see citing works
Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration
Gouwy, M., Struyf, S., Catusse, J., Proost, P., & Van Damme, J. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.1003479 · Cited by 129 · see citing works
High CXCL10 Expression in Rejected Kidneys and Predictive Role of Pretransplant Serum CXCL10 for Acute Rejection And Chronic Allograft Nephropathy
Lazzeri, E., Rotondi, M., Mazzinghi, B., Lasagni, L., Buonamano, A., Rosati, A., Pradella, F., Fossombroni, V., La Villa, G., Gacci, M., et al. (2005) · Transplantation · doi:10.1097/01.tp.0000160759.85080.2e · Cited by 96 · see citing works
High Pretransplant Serum Levels of CXCL10/IP-10 Are Related to Increased Risk of Renal Allograft Failure
Rotondi, M., Rosati, A., Buonamano, A., Lasagni, L., Lazzeri, E., Pradella, F., Fossombroni, V., Cirami, C., Liotta, F., La Villa, G., et al. (2004) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2004.00525.x · Cited by 92 · see citing works
Combination of CCR1 mRNA, MCP1, and CA125 Measurements in Peripheral Blood as a Diagnostic Test for Endometriosis
Agic, A., Djalali, S., Wolfler, M. M., Halis, G., Diedrich, K., & Hornung, D. (2008) · Reproductive Sciences · doi:10.1177/1933719108318598 · Cited by 88 · see citing works
Kras and tumor immunity: friend or foe?
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Self-citation

Authors: Rossi, D., & Zlotnik, A.
Affiliations: Pharmingen Inc., 10975 Torreyana Road, San Diego, California 92121–1111;
ORCID: Zlotnik, Albert
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2000-04
Volume: 18
Issue: 1
Pages: 217-242
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev.immunol.18.1.217
OpenAlex: W2118526748
Cited by: 2,410
References: 121
Citations by year: 2026: 13 · 2025: 22 · 2024: 34 · 2023: 28 · 2022: 36 · 2021: 43 · 2020: 41 · 2019: 54 · 2018: 53 · 2017: 66 · 2016: 62 · 2015: 79 · 2014: 89 · 2013: 99 · 2012: 101
FWCI: 15.93
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords: chemokines, chemokine receptors, HIV co-receptor, leukocyte recruitment, inflammation, dendritic cell maturation, T cell development, Th1/Th2 immune response, angiogenesis, tumor growth, metastasis, therapeutic target
MeSH terms: Animals, Bone Marrow, Homeostasis, Humans, Lymphoid Tissue, Neoplasm Metastasis, Thymus Gland, Neovascularization, Physiologic, Chemokines, Receptors, Chemokine, Mice

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The Biology of Chemokines and their Receptors

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