Evidence for the existence of a CXCL17 receptor distinct from GPR35

Binti Mohd Amir, N. A.S., Mackenzie, A. E., Jenkins, L. , Boustani, K., Hillier, M. C., Tsuchiya, T., Milligan, G. and Pease, J. E. (2018) Evidence for the existence of a CXCL17 receptor distinct from GPR35. Journal of Immunology, 201(2), pp. 714-724. (doi: 10.4049/jimmunol.1700884) (PMID:29875152) (PMCID:PMC6036231)

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The chemokine CXCL17 is associated with the innate response in mucosal tissues but is poorly characterized. Similarly, the G protein–coupled receptor GPR35, expressed by monocytes and mast cells, has been implicated in the immune response, although its precise role is ill-defined. A recent manuscript reported that GPR35 was able to signal in response to CXCL17, which we set out to confirm in this study. GPR35 was readily expressed using transfection systems but failed to signal in response to CXCL17 in assays of β-arrestin recruitment, inositol phosphate production, calcium flux, and receptor endocytosis. Similarly, in chemotaxis assays, GPR35 did not confirm sensitivity to a range of CXCL17 concentrations above that observed in the parental cell line. We subsequently employed a real time chemotaxis assay (TAXIScan) to investigate the migratory responses of human monocytes and the monocytic cell line THP-1 to a gradient of CXCL17. Freshly isolated human monocytes displayed no obvious migration to CXCL17. Resting THP-1 cells showed a trend toward directional migration along a CXCL17 gradient, which was significantly enhanced by overnight incubation with PGE2. However, pretreatment of PGE2-treated THP-1 cells with the well-characterized GPR35 antagonist ML145 did not significantly impair their migratory responses to CXCL17 gradient. CXCL17 was susceptible to cleavage with chymase, although this had little effect its ability to recruit THP-1 cells. We therefore conclude that GPR35 is unlikely to be a bona fide receptor for CXCL17 and that THP-1 cells express an as yet unidentified receptor for CXCL17.

Item Type:Articles
Additional Information:Also supported by Asthma UK Centre Grant AUK-BC-2015-01 (to J.E.P.)
Glasgow Author(s) Enlighten ID:Milligan, Professor Graeme and Jenkins, Mrs Laura and Mackenzie, Miss Amanda
Authors: Binti Mohd Amir, N. A.S., Mackenzie, A. E., Jenkins, L., Boustani, K., Hillier, M. C., Tsuchiya, T., Milligan, G., and Pease, J. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN (Online):1550-6606
Published Online:06 June 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Journal of Immunology 201(2):714-724
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
726201Defining the functional roles of the enigmatic G protein coupled receptor GPR35Graeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/P000649/1RI MOLECULAR CELL & SYSTEMS BIOLOGY