Inflammatory chemokine receptors support inflammatory macrophage and dendritic cell maturation

Bartolini, R. , Medina-Ruiz, L., Hayes, A. J., Kelly, C. J., Halawa, H. A. and Graham, G. J. (2022) Inflammatory chemokine receptors support inflammatory macrophage and dendritic cell maturation. ImmunoHorizons, 6(11), pp. 743-759. (doi: 10.4049/immunohorizons.2200069) (PMID:36426967)

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Publisher's URL: https://journals.aai.org/immunohorizons/article/6/11/743/237300/Inflammatory-Chemokine-Receptors-Support

Abstract

Dendritic cells form clusters in vivo, but the mechanism behind this has not been determined. In this article, we demonstrate that monocytes from mice deficient in the chemokine receptors CCR1, CCR2, CCR3, and CCR5 display reduced clustering in vitro, which is associated with impaired dendritic cell and macrophage differentiation. We further show that the differentiating cells themselves produce ligands for these receptors that function, in a redundant manner, to regulate cell clustering. Deletion of, or pharmacological blockade of, more than one of these receptors is required to impair clustering and differentiation. Our data show that chemokines and their receptors support clustering by increasing expression of, and activating, cell-surface integrins, which are associated with cell–cell interactions and, in the context of monocyte differentiation, with reduced expression of Foxp1, a known transcriptional suppressor of monocyte differentiation. Our data therefore provide a mechanism whereby chemokines and their receptors typically found in inflammatory environments can interact to promote murine monocyte differentiation to macrophages and dendritic cells.

Item Type:Articles
Additional Information:Work in GJG’s laboratory is funded by a Wellcome Trust Investigator Award (REF: 217093/Z/19/Z) and an MRC Programme Grant (MRV0109721).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kelly, Dr Christopher and Hayes, Mr Alan and Medina-Ruiz, Dr Laura and Bartolini, Mr Robin and Graham, Professor Gerard and Halawa, Heba Adnan M
Authors: Bartolini, R., Medina-Ruiz, L., Hayes, A. J., Kelly, C. J., Halawa, H. A., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:ImmunoHorizons
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in ImmunoHorizons 6(11): 743-759
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306649Defining chemokine receptor involvement in the myelomonocytic inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)217093/Z/19/ZIII - Immunology
308056Placental chemokine compartmentalisation by atypical chemokine receptors.Gerard GrahamMedical Research Council (MRC)MR/V010972/1III - Immunology