Characterising interleukin-27 (IL-27) responses in human blood derived macrophage cells

Thomas Helps; Christa Baker; Heather M. Wilson; Simon Arthur; Graeme I Murray; Mairi H. McLean

doi:10.1016/j.cyto.2025.157097

Characterising interleukin-27 (IL-27) responses in human blood derived macrophage cells

Thomas Helps
, Christa Baker
, Heather M. Wilson
, Simon Arthur
, Graeme I Murray
, Mairi H. McLean^* (Corresponding Author)

^*Corresponding author for this work

University of Dundee

Research output: Contribution to journal › Article › peer-review

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Abstract

Macrophages are key cells in the pathogenesis of chronic inflammatory diseases. Interleukin (IL)-27 is a pleiotropic cytokine with mostly immunoregulatory functions and associated with a wide array of diseases. There is little knowledge on the effects of IL-27 on human macrophages. Here, we characterise the effect of IL-27 on human blood derived CD14+ monocyte derived macrophages (MDMs), in resting state and under inflammatory stimulation (+LPS/PepG), through targeted transcriptomic expression profile, phagocytosis of E. coli bioparticles and expression of intracellular and secreted proteins by DIA mass spectrometry and multiplex ELISA, respectively. There was no change in pro-inflammatory cytokine gene expression with IL-27. IL-27 led to changes in the chemokine secretome, inducing a significant upregulation of the chemokines CXCL9 and CXCL10 and reduced expression of CCL2, CCL7, CCL13, CCL18, CCL24, CXCL13, IL-10 and Midkine. Macrophage phagocytosis was not affected by IL-27. IL-27 effects on intracellular proteome were subtle overall. Using unadjusted p values, changes were most pronounced in the resting state, with a significant (p < 0.05) increase in 106 and decrease in 11 proteins. Enrichment analysis suggested regulation of several biological processes by IL-27, including cellular response to type II interferon. Overall, we demonstrate novel biology of IL-27 mediated effects in human macrophages.

Original language	English
Article number	157097
Number of pages	12
Journal	Cytokine
Volume	198
Early online date	22 Dec 2025
DOIs	https://doi.org/10.1016/j.cyto.2025.157097
Publication status	E-pub ahead of print - 22 Dec 2025

Bibliographical note

The authors thank Gwen Kennedy, Biomarker core facility lab, School of Medicine, University of Dundee for help with the multiplex assays, Susan Bray from the Tayside biorepository for the immunohistochemistry, Dr. Claire Mobbs for IL-27R qPCR analysis and Dr. Molly Scott for CD68 immunostaining of MDMs. The authors thank Dr. Andy Howden, School of Life Sciences, University of Dundee, for help with proteomic data analysis and presentation.

Data Availability Statement

Data will be made available on request.

Funding

This work was funded by PhD studentship to Thomas Helps from The Cunningham Trust (CT-18-15).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Macrophage
Interleukin-27
Chemokine

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Helps_etal_C_Characterising_Interleukin-27_VOR
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https://www.sciencedirect.com/science/article/pii/S1043466625002443

Cite this

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title = "Characterising interleukin-27 (IL-27) responses in human blood derived macrophage cells",

abstract = "Macrophages are key cells in the pathogenesis of chronic inflammatory diseases. Interleukin (IL)-27 is a pleiotropic cytokine with mostly immunoregulatory functions and associated with a wide array of diseases. There is little knowledge on the effects of IL-27 on human macrophages. Here, we characterise the effect of IL-27 on human blood derived CD14+ monocyte derived macrophages (MDMs), in resting state and under inflammatory stimulation (+LPS/PepG), through targeted transcriptomic expression profile, phagocytosis of E. coli bioparticles and expression of intracellular and secreted proteins by DIA mass spectrometry and multiplex ELISA, respectively. There was no change in pro-inflammatory cytokine gene expression with IL-27. IL-27 led to changes in the chemokine secretome, inducing a significant upregulation of the chemokines CXCL9 and CXCL10 and reduced expression of CCL2, CCL7, CCL13, CCL18, CCL24, CXCL13, IL-10 and Midkine. Macrophage phagocytosis was not affected by IL-27. IL-27 effects on intracellular proteome were subtle overall. Using unadjusted p values, changes were most pronounced in the resting state, with a significant (p < 0.05) increase in 106 and decrease in 11 proteins. Enrichment analysis suggested regulation of several biological processes by IL-27, including cellular response to type II interferon. Overall, we demonstrate novel biology of IL-27 mediated effects in human macrophages.",

keywords = "Macrophage, Interleukin-27, Chemokine",

author = "Thomas Helps and Christa Baker and Wilson, \{Heather M.\} and Simon Arthur and Murray, \{Graeme I\} and McLean, \{Mairi H.\}",

note = "The authors thank Gwen Kennedy, Biomarker core facility lab, School of Medicine, University of Dundee for help with the multiplex assays, Susan Bray from the Tayside biorepository for the immunohistochemistry, Dr. Claire Mobbs for IL-27R qPCR analysis and Dr. Molly Scott for CD68 immunostaining of MDMs. The authors thank Dr. Andy Howden, School of Life Sciences, University of Dundee, for help with proteomic data analysis and presentation.",

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AU - McLean, Mairi H.

N1 - The authors thank Gwen Kennedy, Biomarker core facility lab, School of Medicine, University of Dundee for help with the multiplex assays, Susan Bray from the Tayside biorepository for the immunohistochemistry, Dr. Claire Mobbs for IL-27R qPCR analysis and Dr. Molly Scott for CD68 immunostaining of MDMs. The authors thank Dr. Andy Howden, School of Life Sciences, University of Dundee, for help with proteomic data analysis and presentation.

PY - 2025/12/22

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N2 - Macrophages are key cells in the pathogenesis of chronic inflammatory diseases. Interleukin (IL)-27 is a pleiotropic cytokine with mostly immunoregulatory functions and associated with a wide array of diseases. There is little knowledge on the effects of IL-27 on human macrophages. Here, we characterise the effect of IL-27 on human blood derived CD14+ monocyte derived macrophages (MDMs), in resting state and under inflammatory stimulation (+LPS/PepG), through targeted transcriptomic expression profile, phagocytosis of E. coli bioparticles and expression of intracellular and secreted proteins by DIA mass spectrometry and multiplex ELISA, respectively. There was no change in pro-inflammatory cytokine gene expression with IL-27. IL-27 led to changes in the chemokine secretome, inducing a significant upregulation of the chemokines CXCL9 and CXCL10 and reduced expression of CCL2, CCL7, CCL13, CCL18, CCL24, CXCL13, IL-10 and Midkine. Macrophage phagocytosis was not affected by IL-27. IL-27 effects on intracellular proteome were subtle overall. Using unadjusted p values, changes were most pronounced in the resting state, with a significant (p < 0.05) increase in 106 and decrease in 11 proteins. Enrichment analysis suggested regulation of several biological processes by IL-27, including cellular response to type II interferon. Overall, we demonstrate novel biology of IL-27 mediated effects in human macrophages.

AB - Macrophages are key cells in the pathogenesis of chronic inflammatory diseases. Interleukin (IL)-27 is a pleiotropic cytokine with mostly immunoregulatory functions and associated with a wide array of diseases. There is little knowledge on the effects of IL-27 on human macrophages. Here, we characterise the effect of IL-27 on human blood derived CD14+ monocyte derived macrophages (MDMs), in resting state and under inflammatory stimulation (+LPS/PepG), through targeted transcriptomic expression profile, phagocytosis of E. coli bioparticles and expression of intracellular and secreted proteins by DIA mass spectrometry and multiplex ELISA, respectively. There was no change in pro-inflammatory cytokine gene expression with IL-27. IL-27 led to changes in the chemokine secretome, inducing a significant upregulation of the chemokines CXCL9 and CXCL10 and reduced expression of CCL2, CCL7, CCL13, CCL18, CCL24, CXCL13, IL-10 and Midkine. Macrophage phagocytosis was not affected by IL-27. IL-27 effects on intracellular proteome were subtle overall. Using unadjusted p values, changes were most pronounced in the resting state, with a significant (p < 0.05) increase in 106 and decrease in 11 proteins. Enrichment analysis suggested regulation of several biological processes by IL-27, including cellular response to type II interferon. Overall, we demonstrate novel biology of IL-27 mediated effects in human macrophages.

KW - Macrophage

KW - Interleukin-27

KW - Chemokine

U2 - 10.1016/j.cyto.2025.157097

DO - 10.1016/j.cyto.2025.157097

M3 - Article

C2 - 41435503

SN - 1043-4666

VL - 198

JO - Cytokine

JF - Cytokine

M1 - 157097

ER -

Characterising interleukin-27 (IL-27) responses in human blood derived macrophage cells

Abstract

Bibliographical note

Data Availability Statement

Funding

UN SDGs

Keywords

Access to Document

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