Key Points
-
Chemokines are small, secreted proteins with leukocyte chemoattractant and cytokine-like activities that are mediated by a distinct subfamily of G-protein-coupled receptors (GPCRs). As described in this Review, humans and viruses have evolved numerous strategies to elude chemokine activities and divert leukocyte recruitment.
-
Seven-transmembrane domain receptors that have high sequence similarity to chemokine receptors that bind chemokines with high affinity but do not elicit migration or conventional signalling have been described. This subfamily of silent or decoy receptors includes the chemokine receptors Duffy antigen receptor for chemokines (DARC), D6 and CCX-CKR.
-
Chemokine decoy receptors recognize distinct and complementary sets of ligands and are strategically expressed by different cell types. In vitro and in vivo data indicate that they dampen local inflammation.
-
Viruses and parasites have evolved multiple strategies to elude chemoattractants, including the expression of soluble and seven-transmembrane domain decoy receptors.
Abstract
A set of chemokine receptors are structurally unable to elicit migration or conventional signalling responses after ligand engagement. These 'silent' (non-signalling) chemokine receptors regulate inflammatory and immune reactions in different ways, including by acting as decoys and scavengers. Chemokine decoy receptors recognize distinct and complementary sets of ligands and are strategically expressed in different cellular contexts. Importantly, viruses and parasites have evolved multiple strategies to elude chemokines, including the expression of decoy receptors. So, decoy receptors for chemokines represent a general strategy to tune, shape and temper innate and adaptive immunity.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Luster, A. D. Chemokines — chemotactic cytokines that mediate inflammation. N. Engl. J. Med. 338, 436–445 (1998).
Charo, I. F. & Ransohoff, R. M. The many roles of chemokines and chemokine receptors in inflammation. N. Engl. J. Med. 354, 610–621 (2006).
Rollins, B. J. Chemokines. Blood 90, 909–928 (1997).
Mantovani, A. The chemokine system: redundancy for robust outputs. Immunol. Today 20, 254–257 (1999).
Murphy, P. M. The molecular biology of leukocyte chemoattractant receptors. Annu. Rev. Immunol. 12, 593–633 (1994).
Mantovani, A., Locati, M., Vecchi, A., Sozzani, S. & Allavena, P. Decoy receptors: a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol. 22, 328–336 (2001).
Horuk, R. et al. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science 261, 1182–1184 (1993). This paper showed that the Duffy blood group antigen is the erythrocyte receptor for chemokines.
Bonini, J. A. et al. Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3. DNA Cell Biol. 16, 1249–1256 (1997).
Nibbs, R. J., Wylie, S. M., Yang, J., Landau, N. R. & Graham, G. J. Cloning and characterization of a novel promiscuous human β-chemokine receptor D6. J. Biol. Chem. 272, 32078–32083 (1997).
Gosling, J. et al. Identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK. J. Immunol. 164, 2851–2856 (2000).
Miller, L. H., Mason, S. J., Clyde, D. F. & McGinniss, M. H. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N. Engl. J. Med. 295, 302–304 (1976).
Peiper, S. C. et al. The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. J. Exp. Med. 181, 1311–1317 (1995).
Hadley, T. J. & Peiper, S. C. From malaria to chemokine receptor: the emerging physiologic role of the Duffy blood group antigen. Blood 89, 3077–3091 (1997).
Rot, A. Contribution of Duffy antigen to chemokine function. Cytokine Growth Factor Rev. 16, 687–694 (2005).
Chaudhuri, A. et al. Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite. Proc. Natl Acad. Sci. USA 90, 10793–10797 (1993).
Choe, H. et al. Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC). Mol. Microbiol. 55, 1413–1422 (2005).
Tournamille, C. et al. Structure–function analysis of the extracellular domains of the Duffy antigen/receptor for chemokines: characterization of antibody and chemokine binding sites. Br. J. Haematol. 122, 1014–1023 (2003).
Chitnis, C. E., Chaudhuri, A., Horuk, R., Pogo, A. O. & Miller, L. H. The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasites to erythrocytes. J. Exp. Med. 184, 1531–1536 (1996).
Gardner, L., Patterson, A. M., Ashton, B. A., Stone, M. A. & Middleton, J. The human Duffy antigen binds selected inflammatory but not homeostatic chemokines. Biochem. Biophys. Res. Commun. 321, 306–312 (2004).
Neote, K., Mak, J. Y., Kolakowski, L. F. Jr & Schall, T. J. Functional and biochemical analysis of the cloned Duffy antigen: identity with the red blood cell chemokine receptor. Blood 84, 44–52 (1994).
Lee, J. S. et al. Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. J. Immunol. 170, 5244–5251 (2003).
Middleton, J. et al. Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 91, 385–395 (1997).
Dawson, T. C. et al. Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). Blood 96, 1681–1684 (2000).
Kashiwazaki, M. et al. A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions. Int. Immunol. 15, 1219–1227 (2003).
Darbonne, W. C. et al. Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin. J. Clin. Invest. 88, 1362–1369 (1991).
Du, J. et al. Potential role for Duffy antigen chemokine-binding protein in angiogenesis and maintenance of homeostasis in response to stress. J. Leukoc. Biol. 71, 141–153 (2002).
Addison, C. L., Belperio, J. A., Burdick, M. D. & Strieter, R. M. Overexpression of the Duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis. BMC Cancer 4, 28 (2004).
Wang, J. et al. Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Oncogene 19 June 2006 (doi:10.1038/sj.onc.1209703).
Shen, H., Schuster, R., Stringer, K. F., Waltz, S. E. & Lentsch, A. B. The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth. FASEB J. 20, 59–64 (2006).
Bandyopadhyay, S. et al. Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nature Med. 12, 933–938 (2006).
Rios, M. et al. New genotypes in Fy(a− b−) individuals: nonsense mutations (Trp to stop) in the coding sequence of either FY A or FY B. Br. J. Haematol. 108, 448–454 (2000).
Lentsch, A. B. The Duffy antigen/receptor for chemokines (DARC) and prostate cancer. A role as clear as black and white? FASEB J. 16, 1093–1095 (2002).
Segerer, S. et al. When renal allografts turn DARC. Transplantation 75, 1030–1034 (2003).
Danoff, T. M., Hallows, K. R., Brayman, K. L. & Feldman, H. I. Renal allograft survival in African-Americans: influence of the Duffy blood group. Transplantation 67, S8 (1999).
Akalin, E. & Neylan, J. F. The influence of Duffy blood group on renal allograft outcome in African Americans. Transplantation 75, 1496–1500 (2003).
Mange, K. C. et al. Duffy antigen receptor and genetic susceptibility of African Americans to acute rejection and delayed function. Kidney Int. 66, 1187–1192 (2004).
Nibbs, R. J., Wylie, S. M., Pragnell, I. B. & Graham, G. J. Cloning and characterization of a novel murine β chemokine receptor, D6. Comparison to three other related macrophage inflammatory protein-1α receptors, CCR-1, CCR-3, and CCR-5. J. Biol. Chem. 272, 12495–12504 (1997).
Fra, A. M. et al. Scavenging of inflammatory CC chemokines by the promiscuous putatively silent chemokine receptor D6. J. Immunol. 170, 2279–2282 (2003). This paper provided the first in vitro evidence that D6 acts as a decoy and scavenger receptor for inflammatory CC-chemokines.
Nibbs, R. J., Yang, J., Landau, N. R., Mao, J. H. & Graham, G. J. LD78β, a non-allelic variant of human MIP-1α (LD78α), has enhanced receptor interactions and potent HIV suppressive activity. J. Biol. Chem. 274, 17478–17483 (1999).
Bonecchi, R. et al. Differential recognition and scavenging of native and truncated macrophage-derived chemokine (MDC/CCL22) by the D6 decoy receptor. J. Immunol. 172, 4972–4976 (2004).
Nibbs, R. J. et al. The β-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. Am. J. Pathol. 158, 867–877 (2001). This is the first study showing D6 expression by human lymphatic endothelial cells.
Graham, G. J. & McKimmie, C. S. Chemokine scavenging by D6: a movable feast? Trends Immunol. 27, 381–386 (2006).
Martinez de la Torre, Y. et al. Increased inflammation in mice deficient for the chemokine decoy receptor D6. Eur. J. Immunol. 35, 1342–1346 (2005).
Blackburn, P. E. et al. Purification and biochemical characterization of the D6 chemokine receptor. Biochem. J. 379, 263–272 (2004).
Weber, M. et al. The chemokine receptor D6 constitutively traffics to and from the cell surface to internalize and degrade chemokines. Mol. Biol. Cell 15, 2492–2508 (2004).
Galliera, E. et al. β-Arrestin dependent constitutive internalization of the human chemokine decoy receptor D6. J. Biol. Chem. 279, 25590–25597 (2004).
Neil, S. J. et al. The promiscuous CC chemokine receptor D6 is a functional coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and HIV-2 on astrocytes. J. Virol. 79, 9618–9624 (2005).
Jamieson, T. et al. The chemokine receptor D6 limits the inflammatory response in vivo. Nature Immunol. 6, 403–411 (2005). References 43 and 48 provided the first in vivo demonstration that D6 dampens local inflammation.
Liu, L. et al. The silent chemokine receptor D6 is required for generating T cell responses that mediate experimental autoimmune encephalomyelitis. J. Immunol. 177, 17–21 (2006).
Townson, J. R. & Nibbs, R. J. Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3β/mCCL19: comparison to human CCX-CKR. Eur. J. Immunol. 32, 1230–1241 (2002).
Comerford, I., Milasta, S., Morrow, V., Milligan, G. & Nibbs, R. The chemokine receptor CCX-CKR mediates effective scavenging of CCL19 in vitro. Eur. J. Immunol. 36, 1904–1916 (2006).
Muller, G., Hopken, U. E. & Lipp, M. The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity. Immunol. Rev. 195, 117–135 (2003).
Sallusto, F. et al. Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur. J. Immunol. 29, 1617–1625 (1999).
Perrier, P. et al. Distinct transcriptional programs activated by interleukin-10 with or without lipopolysaccharide in dendritic cells: induction of the B cell-activating chemokine, CXC chemokine ligand 13. J. Immunol. 172, 7031–7042 (2004).
Samson, M., Soularue, P., Vassart, G. & Parmentier, M. The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1–CMKBR5) are clustered in the p21.3–p24 region of chromosome 3. Genomics 36, 522–526 (1996).
Fan, P. et al. Cloning and characterization of a novel human chemokine receptor. Biochem. Biophys. Res. Commun. 243, 264–268 (1998).
Migeotte, I., Franssen, J. D., Goriely, S., Willems, F. & Parmentier, M. Distribution and regulation of expression of the putative human chemokine receptor HCR in leukocyte populations. Eur. J. Immunol. 32, 494–501 (2002).
Biber, K., Zuurman, M. W., Homan, H. & Boddeke, H. W. Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2, CCL5, CCL7, and CCL8. J. Leukoc. Biol. 74, 243–251 (2003).
D'Amico, G. et al. Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys. Nature Immunol. 1, 387–391 (2000).
Dar, A. et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nature Immunol. 6, 1038–1046 (2005).
Mahad, D. et al. Modulating CCR2 and CCL2 at the blood–brain barrier: relevance for multiple sclerosis pathogenesis. Brain 129, 212–223 (2006).
Tylaska, L. A. et al. Ccr2 regulates the level of MCP-1/CCL2 in vitro and at inflammatory sites and controls T cell activation in response to alloantigen. Cytokine 18, 184–190 (2002).
Finlay, B. B. & McFadden, G. Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124, 767–782 (2006).
Spriggs, M. K. et al. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Cell 71, 145–152 (1992).
Alcami, A. & Smith, G. L. A soluble receptor for interleukin-1β encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71, 153–167 (1992).
Smith, C. A. et al. T2 open reading frame from the Shope fibroma virus encodes a soluble form of the TNF receptor. Biochem. Biophys. Res. Commun. 176, 335–342 (1991). References 64–66 described the first virally encoded cytokine decoy receptors.
Upton, C., Mossman, K. & McFadden, G. Encoding of a homolog of the IFN-γ receptor by myxoma virus. Science 258, 1369–1372 (1992).
Colotta, F. et al. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science 261, 472–475 (1993). This is the first demonstration of a cellular decoy receptor inhibiting IL-1 activity.
Murphy, P. M. Viral exploitation and subversion of the immune system through chemokine mimicry. Nature Immunol. 2, 116–122 (2001).
Alcami, A. Viral mimicry of cytokines, chemokines and their receptors. Nature Rev. Immunol. 3, 36–50 (2003).
Boomker, J. M., de Leij, L. F., The, T. H. & Harmsen, M. C. Viral chemokine-modulatory proteins: tools and targets. Cytokine Growth Factor Rev. 16, 91–103 (2005).
Damon, I., Murphy, P. M. & Moss, B. Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog. Proc. Natl Acad. Sci. USA 95, 6403–6407 (1998).
Sozzani, S. et al. The viral chemokine macrophage inflammatory protein-II is a selective TH2 chemoattractant. Blood 92, 4036–4039 (1998).
Lalani, A. S. et al. The purified myxoma virus γ interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines. J. Virol. 71, 4356–4363 (1997).
Mossman, K. et al. Myxoma virus M-T7, a secreted homolog of the interferon-γ receptor, is a critical virulence factor for the development of myxomatosis in European rabbits. Virology 215, 17–30 (1996).
Graham, K. A. et al. The T1/35kDa family of poxvirus-secreted proteins bind chemokines and modulate leukocyte influx into virus-infected tissues. Virology 229, 12–24 (1997).
Smith, C. A. et al. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits β chemokine activity yet lacks sequence homology to known chemokine receptors. Virology 236, 316–327 (1997).
Lucas, A. & McFadden, G. Secreted immunomodulatory viral proteins as novel biotherapeutics. J. Immunol. 173, 4765–4774 (2004).
Alejo, A. et al. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus. Proc. Natl Acad. Sci. USA 103, 5995–6000 (2006).
Parry, C. M. et al. A broad spectrum secreted chemokine binding protein encoded by a herpesvirus. J. Exp. Med. 191, 573–578 (2000).
Alexander, J. M. et al. Structural basis of chemokine sequestration by a herpesvirus decoy receptor. Cell 111, 343–356 (2002).
Alcami, A. Structural basis of the herpesvirus M3–chemokine interaction. Trends Microbiol. 11, 191–192 (2003).
Webb, L. M., Smith, V. P. & Alcami, A. The γherpesvirus chemokine binding protein can inhibit the interaction of chemokines with glycosaminoglycans. FASEB J. 18, 571–573 (2004).
van Berkel, V. et al. Critical role for a high-affinity chemokine-binding protein in γ-herpesvirus-induced lethal meningitis. J. Clin. Invest. 109, 905–914 (2002).
Bridgeman, A., Stevenson, P. G., Simas, J. P. & Efstathiou, S. A secreted chemokine binding protein encoded by murine γherpesvirus-68 is necessary for the establishment of a normal latent load. J. Exp. Med. 194, 301–312 (2001).
Jensen, K. K. et al. Disruption of CCL21-induced chemotaxis in vitro and in vivo by M3, a chemokine-binding protein encoded by murine γherpesvirus 68. J. Virol. 77, 624–630 (2003).
Wang, D., Bresnahan, W. & Shenk, T. Human cytomegalovirus encodes a highly specific RANTES decoy receptor. Proc. Natl Acad. Sci. USA 101, 16642–16647 (2004).
Bryant, N. A., Davis-Poynter, N., Vanderplasschen, A. & Alcami, A. Glycoprotein G isoforms from some αherpesviruses function as broad-spectrum chemokine binding proteins. EMBO J. 22, 833–846 (2003).
Reading, P. C., Symons, J. A. & Smith, G. L. A soluble chemokine-binding protein from vaccinia virus reduces virus virulence and the inflammatory response to infection. J. Immunol. 170, 1435–1442 (2003).
Gao, J. L. & Murphy, P. M. Human cytomegalovirus open reading frame US28 encodes a functional β chemokine receptor. J. Biol. Chem. 269, 28539–28542 (1994).
Kuhn, D. E., Beall, C. J. & Kolattukudy, P. E. The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity. Biochem. Biophys. Res. Commun. 211, 325–330 (1995).
Casarosa, P. et al. Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J. Biol. Chem. 276, 1133–1137 (2001).
Bodaghi, B. et al. Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells. J. Exp. Med. 188, 855–866 (1998). This paper shows that human cytomegalovirus encodes a chemokine receptor (US28) that can scavenge chemokines.
Randolph-Habecker, J. R. et al. The expression of the cytomegalovirus chemokine receptor homolog US28 sequesters biologically active CC chemokines and alters IL-8 production. Cytokine 19, 37–46 (2002).
Fraile-Ramos, A. et al. The human cytomegalovirus US28 protein is located in endocytic vesicles and undergoes constitutive endocytosis and recycling. Mol. Biol. Cell 12, 1737–1749 (2001).
Mokros, T. et al. Surface expression and endocytosis of the human cytomegalovirus-encoded chemokine receptor US28 is regulated by agonist-independent phosphorylation. J. Biol. Chem. 277, 45122–45128 (2002).
Billstrom, M. A., Johnson, G. L., Avdi, N. J. & Worthen, G. S. Intracellular signaling by the chemokine receptor US28 during human cytomegalovirus infection. J. Virol. 72, 5535–5544 (1998).
Droese, J. et al. HCMV-encoded chemokine receptor US28 employs multiple routes for internalization. Biochem. Biophys. Res. Commun. 322, 42–49 (2004).
Fraile-Ramos, A., Kohout, T. A., Waldhoer, M. & Marsh, M. Endocytosis of the viral chemokine receptor US28 does not require β-arrestins but is dependent on the clathrin-mediated pathway. Traffic 4, 243–253 (2003).
Milne, R. S. et al. RANTES binding and down-regulation by a novel human herpesvirus-6 β chemokine receptor. J. Immunol. 164, 2396–2404 (2000).
Smith, P. et al. Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity. J. Exp. Med. 202, 1319–1325 (2005).
Klein, D. E., Nappi, V. M., Reeves, G. T., Shvartsman, S. Y. & Lemmon, M. A. Argos inhibits epidermal growth factor receptor signalling by ligand sequestration. Nature 430, 1040–1044 (2004).
Proudfoot, A. E. Chemokine receptors: multifaceted therapeutic targets. Nature Rev. Immunol. 2, 106–115 (2002).
Zlotnik, A. & Yoshie, O. Chemokines: a new classification system and their role in immunity. Immunity 12, 121–127 (2000).
Johnson, Z., Proudfoot, A. E. & Handel, T. M. Interaction of chemokines and glycosaminoglycans: a new twist in the regulation of chemokine function with opportunities for therapeutic intervention. Cytokine Growth Factor Rev. 16, 625–636 (2005).
Ariel, A. et al. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nature Immunol. 7, 1209–1216 (2006).
Acknowledgements
We thank M. Necci for graphical assistance. This work was supported by the Italian Association for Cancer Research, the Italian Ministry of University and Research (FIRB, COFIN and CNR funding), the Italian Ministry of Health, Fondazione Cariplo (NOBEL project), the European Commission (NNOCHEM project and Mugen project), and the Istituto Superiore della Sanità (AIDS project).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Related links
Related links
DATABASES
Entrez Genome
OMIM
FURTHER INFORMATION
Cytokine Family cDNA Database (dbCFC)
HUGO Gene Nomenclature Committee
Glossary
- G-protein-coupled receptor
-
(GPCR). A receptor that comprises seven membrane-spanning helical segments, which are connected by extracellular and intracellular loops. These receptors associate with G-proteins, which are a family of trimeric, intracellular signalling proteins with common β- and γ-chains, and one of several α-chains. The α-chain determines the nature of the signal that is transmitted from a ligand-occupied GPCR to downstream effector systems.
- Decoy receptors
-
The classic definition of a receptor involves ligand recognition and signalling. Decoy receptors recognize ligands with high affinity and specificity but fail to elicit a response, thereby acting as a molecular trap for the ligand and in some cases as dominant negatives for key components of the signalling receptor complex.
- Scavenger receptors
-
Scavenger receptors were originally defined in macrophages and endothelial cells as any of a structurally diverse group of receptors with an ability to bind polyanionic ligands such as oxidized low-density lipoprotein, as occurs in atherosclerotic plaques. Most scavenger receptors also bind either microbial ligands or apoptotic cells. In a broader, more general sense, scavenger receptors are transmembrane molecules that are devoted to mopping up ligands.
- DRY motif
-
An amino-acid motif composed of aspartic acid (D), arginine (R) and tyrosine (Y). It is highly conserved among G-protein-coupled receptors and is thought to be essential for G-protein-mediated signalling.
- Tetraspanins
-
The tetraspanin family contains proteins that span the membrane four times with two exoplasmic loops, and that can be found at the cell surface. Whereas some are highly restricted to specific tissues, others are widely distributed. Members of this family have been implicated in cell activation and proliferation, adhesion, motility, differentiation, and cancer.
- Senescence
-
A nearly irreversible stage of permanent G1 cell-cycle arrest, which is linked to morphological changes (flattening of the cells), metabolic changes and changes in gene expression.
- Orphan receptor
-
A receptor without a known ligand.
- Molecular mimicry
-
The presence of viral proteins that have a primary amino-acid sequence and structure that is related to those of host proteins, indicating that viruses might have 'captured' genes from the host during evolution.
Rights and permissions
About this article
Cite this article
Mantovani, A., Bonecchi, R. & Locati, M. Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol 6, 907–918 (2006). https://doi.org/10.1038/nri1964
Issue Date:
DOI: https://doi.org/10.1038/nri1964
This article is cited by
-
The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention
Cellular & Molecular Immunology (2023)
-
The immunological function of CXCR2 in the liver during sepsis
Journal of Inflammation (2022)
-
GPR182 limits antitumor immunity via chemokine scavenging in mouse melanoma models
Nature Communications (2022)
-
Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer
Nature Communications (2022)
-
A negative-feedback loop maintains optimal chemokine concentrations for directional cell migration
Nature Cell Biology (2020)