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Chemokine Receptor Redundancy and Specificity Are Context Dependent.
Immunity 2019; 50(2):378-389.e5I

Abstract

Currently, we lack an understanding of the individual and combinatorial roles for chemokine receptors in the inflammatory process. We report studies on mice with a compound deletion of Ccr1, Ccr2, Ccr3, and Ccr5, which together control monocytic and eosinophilic recruitment to resting and inflamed sites. Analysis of resting tissues from these mice, and mice deficient in each individual receptor, provides clear evidence for redundant use of these receptors in establishing tissue-resident monocytic cell populations. In contrast, analysis of cellular recruitment to inflamed sites provides evidence of specificity of receptor use for distinct leukocyte subtypes and no indication of comprehensive redundancy. We find no evidence of involvement of any of these receptors in the recruitment of neutrophils or lymphocytes to resting or acutely inflamed tissues. Our data shed important light on combinatorial inflammatory chemokine receptor function and highlight Ccr2 as the primary driver of myelomonocytic cell recruitment in acutely inflamed contexts.

Authors+Show Affiliations

Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK. Electronic address: gerard.graham@glasgow.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30784579

Citation

Dyer, Douglas P., et al. "Chemokine Receptor Redundancy and Specificity Are Context Dependent." Immunity, vol. 50, no. 2, 2019, pp. 378-389.e5.
Dyer DP, Medina-Ruiz L, Bartolini R, et al. Chemokine Receptor Redundancy and Specificity Are Context Dependent. Immunity. 2019;50(2):378-389.e5.
Dyer, D. P., Medina-Ruiz, L., Bartolini, R., Schuette, F., Hughes, C. E., Pallas, K., ... Graham, G. J. (2019). Chemokine Receptor Redundancy and Specificity Are Context Dependent. Immunity, 50(2), pp. 378-389.e5. doi:10.1016/j.immuni.2019.01.009.
Dyer DP, et al. Chemokine Receptor Redundancy and Specificity Are Context Dependent. Immunity. 2019 02 19;50(2):378-389.e5. PubMed PMID: 30784579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemokine Receptor Redundancy and Specificity Are Context Dependent. AU - Dyer,Douglas P, AU - Medina-Ruiz,Laura, AU - Bartolini,Robin, AU - Schuette,Fabian, AU - Hughes,Catherine E, AU - Pallas,Kenneth, AU - Vidler,Francesca, AU - Macleod,Megan K L, AU - Kelly,Christopher J, AU - Lee,Kit Ming, AU - Hansell,Christopher A H, AU - Graham,Gerard J, PY - 2018/05/01/received PY - 2018/11/16/revised PY - 2019/01/22/accepted PY - 2019/2/21/entrez PY - 2019/2/21/pubmed PY - 2019/8/14/medline KW - chemokines KW - dendritic cells KW - inflammation KW - monocytes KW - mouse models KW - receptors SP - 378 EP - 389.e5 JF - Immunity JO - Immunity VL - 50 IS - 2 N2 - Currently, we lack an understanding of the individual and combinatorial roles for chemokine receptors in the inflammatory process. We report studies on mice with a compound deletion of Ccr1, Ccr2, Ccr3, and Ccr5, which together control monocytic and eosinophilic recruitment to resting and inflamed sites. Analysis of resting tissues from these mice, and mice deficient in each individual receptor, provides clear evidence for redundant use of these receptors in establishing tissue-resident monocytic cell populations. In contrast, analysis of cellular recruitment to inflamed sites provides evidence of specificity of receptor use for distinct leukocyte subtypes and no indication of comprehensive redundancy. We find no evidence of involvement of any of these receptors in the recruitment of neutrophils or lymphocytes to resting or acutely inflamed tissues. Our data shed important light on combinatorial inflammatory chemokine receptor function and highlight Ccr2 as the primary driver of myelomonocytic cell recruitment in acutely inflamed contexts. SN - 1097-4180 UR - https://www.unboundmedicine.com/medline/citation/30784579/Chemokine_Receptor_Redundancy_and_Specificity_Are_Context_Dependent L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7613(19)30032-9 DB - PRIME DP - Unbound Medicine ER -