Defining inflammatory chemokine dynamics in embryonic and adult tissues

Koumbas Foley, Lily (2026) Defining inflammatory chemokine dynamics in embryonic and adult tissues. PhD thesis, University of Glasgow.

Abstract

Chemokines orchestrate immune cell migration via interaction with their specific cognate receptors during both homeostasis and inflammation. The inflammatory CC-chemokine receptors CCR1, CCR2, CCR3 and CCR5 (iCCRs) are predominantly expressed by myeloid cells. These receptors exhibit high promiscuity, binding to multiple CCchemokines, which themselves can engage various receptors, creating a complex and dynamic signalling network. iCCRs share ligands with ACKR2, an atypical, non-signalling chemokine receptor. ACKR2 functions as a scavenger of inflammatory chemokines that signal through chemokine receptors CCR1-5, modulating chemokine availability and contributing to the resolution of inflammation. ACKR2 is highly expressed by trophoblasts and lymphatic endothelial cells. ACKR2 expressed by trophoblasts prevents maternal inflammatory chemokines from entering the embryo circulation. In ACKR2-deficient mice, transfer of maternal chemokines disrupts leukocyte distribution in embryonic tissues. In particular a novel F4/80int macrophage subset is reduced in embryonic skin, highlighting emerging roles for inflammatory chemokine signalling in embryogenesis.

This thesis extends these findings by mapping chemokine expression in embryonic tissues and characterising inflammatory chemokine receptor profiles on embryonic myeloid subsets. Homeostatic CXC-chemokines were robustly detected across tissues analysed. Inflammatory chemokines and receptors were more highly detected in the lung and skin than the liver and heart, with particularly high CCL11 expression detected in the lung. This suggests a broader role for inflammatory chemokines in embryonic development. Furthermore, this thesis determines whether macrophage distribution is altered in naïve adult ACKR2-deficient mice. We found that specific subsets of macrophages across multiple adult tissues were reduced in numbers in ACKR2-deficient mice. This could not be attributed to altered cell recruitment caused by dysregulated chemokine levels and also had functional consequences in bacterial infection. Transcriptomic data of lung macrophages demonstrated that ACKR2 has limited effects on gene expression profiles of macrophage populations. Together, these findings indicate that inflammatory chemokine expression in the embryo is tightly regulated and patterned, suggesting important and specific roles, and highlight that ACKR2 expression impacts macrophage numbers beyond the embryo.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology > QR180 Immunology; R Medicine > RC Internal medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: Graham, Professor Gerard
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-85910
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 01 May 2026 10:54
• Last Modified: 05 May 2026 10:09
• Thesis DOI: 10.5525/gla.thesis.85910
• URI: https://theses.gla.ac.uk/id/eprint/85910

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