Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injury

Abstract Objectives The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post‐burn. Methods Flow cytometry was used to measure 25 cell markers, chemokines and cytokines which reflected both pro‐inflammatory and anti‐inflammatory immune...

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Main Authors: Donna Langley, Kate Zimmermann, Emma Krenske, Giorgio Stefanutti, Roy M Kimble, Andrew JA Holland, Mark W Fear, Fiona M Wood, Tony Kenna, Leila Cuttle
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Clinical & Translational Immunology
Subjects:
Online Access:https://doi.org/10.1002/cti2.1496
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author Donna Langley
Kate Zimmermann
Emma Krenske
Giorgio Stefanutti
Roy M Kimble
Andrew JA Holland
Mark W Fear
Fiona M Wood
Tony Kenna
Leila Cuttle
author_facet Donna Langley
Kate Zimmermann
Emma Krenske
Giorgio Stefanutti
Roy M Kimble
Andrew JA Holland
Mark W Fear
Fiona M Wood
Tony Kenna
Leila Cuttle
author_sort Donna Langley
collection DOAJ
description Abstract Objectives The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post‐burn. Methods Flow cytometry was used to measure 25 cell markers, chemokines and cytokines which reflected both pro‐inflammatory and anti‐inflammatory immune profiles. Peripheral blood mononuclear cells from 6 paediatric burn patients who had returned for repeated burn and scar treatments for > 4 timepoints within 12 months post‐burn were compared to four age‐matched healthy controls. Results While overall proportions of T cells, NK cells and macrophages remained relatively constant, over time percentages of these immune cells differentiated into effector and proinflammatory cell phenotypes including Th17 and activated γδ T cells. Circulating proportions of γδ T cells increased their expression of pro‐inflammatory mediators throughout the burn recovery, with a 3–6 fold increase of IL‐17 at 1–3 weeks, and NFκβ 9–18 months post‐burn. T‐regulatory cell plasticity was also observed, and Treg phenotype proportions changed from systemically reduced skin‐homing T‐regs (CCR4+) and increased inflammatory (CCR6+) at 1‐month post‐burn, to double‐positive cell types (CCR4+CCR6+) elevated in circulation for 18 months post‐burn. Furthermore, Tregs were observed to proportionally express less IL‐10 but increased TNF‐α over 18 months. Conclusion Overall, these results indicate the circulating percentages of immune cells do not increase or decrease over time post‐burn, instead they become highly specialised, inflammatory and skin‐homing. In this patient population, these changes persisted for at least 18 months post‐burn, this ‘immune distraction’ may limit the ability of immune cells to prioritise other threats post‐burn, such as respiratory infections.
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spelling doaj.art-53a8ff0570684753971d4a1b3d19a5aa2024-03-25T12:08:33ZengWileyClinical & Translational Immunology2050-00682024-01-01133n/an/a10.1002/cti2.1496Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injuryDonna Langley0Kate Zimmermann1Emma Krenske2Giorgio Stefanutti3Roy M Kimble4Andrew JA Holland5Mark W Fear6Fiona M Wood7Tony Kenna8Leila Cuttle9School of Biomedical Sciences, Faculty of Health Queensland University of Technology (QUT) South Brisbane QLD AustraliaSchool of Biomedical Sciences, Faculty of Health Queensland University of Technology (QUT) South Brisbane QLD AustraliaSchool of Biomedical Sciences, Faculty of Health Queensland University of Technology (QUT) South Brisbane QLD AustraliaDepartment of Paediatric Surgery, Urology, Burns and Trauma Children's Health Queensland, Queensland Children's Hospital South Brisbane QLD AustraliaDepartment of Paediatric Surgery, Urology, Burns and Trauma Children's Health Queensland, Queensland Children's Hospital South Brisbane QLD AustraliaThe Children's Hospital at Westmead Burns Unit, Department of Paediatrics and Child Health, Kids Research Institute Sydney Medical School, The University of Sydney Sydney NSW AustraliaBurn Injury Research Unit, School of Biomedical Sciences The University of Western Australia Perth WA AustraliaBurn Injury Research Unit, School of Biomedical Sciences The University of Western Australia Perth WA AustraliaSchool of Biomedical Sciences, Faculty of Health Queensland University of Technology (QUT) South Brisbane QLD AustraliaSchool of Biomedical Sciences, Faculty of Health Queensland University of Technology (QUT) South Brisbane QLD AustraliaAbstract Objectives The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post‐burn. Methods Flow cytometry was used to measure 25 cell markers, chemokines and cytokines which reflected both pro‐inflammatory and anti‐inflammatory immune profiles. Peripheral blood mononuclear cells from 6 paediatric burn patients who had returned for repeated burn and scar treatments for > 4 timepoints within 12 months post‐burn were compared to four age‐matched healthy controls. Results While overall proportions of T cells, NK cells and macrophages remained relatively constant, over time percentages of these immune cells differentiated into effector and proinflammatory cell phenotypes including Th17 and activated γδ T cells. Circulating proportions of γδ T cells increased their expression of pro‐inflammatory mediators throughout the burn recovery, with a 3–6 fold increase of IL‐17 at 1–3 weeks, and NFκβ 9–18 months post‐burn. T‐regulatory cell plasticity was also observed, and Treg phenotype proportions changed from systemically reduced skin‐homing T‐regs (CCR4+) and increased inflammatory (CCR6+) at 1‐month post‐burn, to double‐positive cell types (CCR4+CCR6+) elevated in circulation for 18 months post‐burn. Furthermore, Tregs were observed to proportionally express less IL‐10 but increased TNF‐α over 18 months. Conclusion Overall, these results indicate the circulating percentages of immune cells do not increase or decrease over time post‐burn, instead they become highly specialised, inflammatory and skin‐homing. In this patient population, these changes persisted for at least 18 months post‐burn, this ‘immune distraction’ may limit the ability of immune cells to prioritise other threats post‐burn, such as respiratory infections.https://doi.org/10.1002/cti2.1496burnscytokinesflow cytometryinflammationlymphocytespaediatrics
spellingShingle Donna Langley
Kate Zimmermann
Emma Krenske
Giorgio Stefanutti
Roy M Kimble
Andrew JA Holland
Mark W Fear
Fiona M Wood
Tony Kenna
Leila Cuttle
Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injury
Clinical & Translational Immunology
burns
cytokines
flow cytometry
inflammation
lymphocytes
paediatrics
title Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injury
title_full Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injury
title_fullStr Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injury
title_full_unstemmed Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injury
title_short Unremitting pro‐inflammatory T‐cell phenotypes, and macrophage activity, following paediatric burn injury
title_sort unremitting pro inflammatory t cell phenotypes and macrophage activity following paediatric burn injury
topic burns
cytokines
flow cytometry
inflammation
lymphocytes
paediatrics
url https://doi.org/10.1002/cti2.1496
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