Leucocyte migration is essential for robust immune and inflammatory responses, and plays a critical role in many human diseases. Chemokines, a family of small secreted protein chemoattractants, are of fundamental importance in this process, directing leucocyte trafficking by signalling through heptahelical G-protein-coupled receptors expressed by the migrating cells. However, several mammalian chemokine receptors, including D6 and CCX-CKR (ChemoCentryx chemokine receptor), do not fit existing models of chemokine receptor function, and do not even appear to signal in response to chemokine binding. Instead, these ‘atypical’ chemokine receptors are biochemically specialized for chemokine sequestration, acting to regulate chemokine bioavailability and thereby influence responses through signalling-competent chemokine receptors. This is of critical importance in vivo, as mice lacking D6 show exaggerated cutaneous inflammatory responses and an increased susceptibility to the development of skin cancer. CCX-CKR, on the other hand, is predicted to modulate homoeostatic lymphocyte and dendritic cell trafficking, key migratory events in acquired immune responses that are directed by CCX-CKR-binding chemokines. Thus studies on ‘atypical’ chemokine receptors are revealing functional and biochemical diversity within the chemokine receptor family and providing insights into novel mechanisms of chemokine regulation.
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December 2006
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Conference Article|
October 25 2006
Chemokine sequestration by atypical chemokine receptors
C.A.H. Hansell;
C.A.H. Hansell
1Division of Immunology, Infection and Inflammation, 120 University Place, University of Glasgow, Glasgow G12 8TA, U.K.
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C.V. Simpson;
C.V. Simpson
1Division of Immunology, Infection and Inflammation, 120 University Place, University of Glasgow, Glasgow G12 8TA, U.K.
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R.J.B. Nibbs
R.J.B. Nibbs
1
1Division of Immunology, Infection and Inflammation, 120 University Place, University of Glasgow, Glasgow G12 8TA, U.K.
1To whom correspondence should be addressed (email r.nibbs@clinmed.gla.ac.uk).
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Publisher: Portland Press Ltd
Received:
June 23 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1009–1013.
Article history
Received:
June 23 2006
Citation
C.A.H. Hansell, C.V. Simpson, R.J.B. Nibbs; Chemokine sequestration by atypical chemokine receptors. Biochem Soc Trans 1 December 2006; 34 (6): 1009–1013. doi: https://doi.org/10.1042/BST0341009
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