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

Donna Langley; Kate Zimmermann; Emma Krenske; Giorgio Stefanutti; Roy M Kimble; Andrew Ja Holland; Mark W Fear; Fiona M Wood; Tony Kenna; Leila Cuttle

doi:10.1002/cti2.1496

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

Clin Transl Immunology. 2024 Mar 8;13(3):e1496. doi: 10.1002/cti2.1496. eCollection 2024.

Authors

Donna Langley^{1

2

3}, Kate Zimmermann^{1

2}, Emma Krenske^{1

2}, Giorgio Stefanutti⁴, Roy M Kimble⁴, Andrew Ja Holland⁵, Mark W Fear⁶, Fiona M Wood^{6

7}, Tony Kenna^{1

2}, Leila Cuttle^{1

3}

Affiliations

¹ School of Biomedical Sciences, Faculty of Health Queensland University of Technology (QUT) South Brisbane QLD Australia.
² Centre for Immunology and Infection Control (CIIC) QIMR Berghofer Medical Research Institute, Queensland University of Technology (QUT) Brisbane QLD Australia.
³ Centre for Biomedical Technology (CBT) Queensland University of Technology (QUT) Kelvin Grove QLD Australia.
⁴ Department of Paediatric Surgery, Urology, Burns and Trauma Children's Health Queensland, Queensland Children's Hospital South Brisbane QLD Australia.
⁵ The 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 Australia.
⁶ Burn Injury Research Unit, School of Biomedical Sciences The University of Western Australia Perth WA Australia.
⁷ Burns Service of Western Australia Perth Children's Hospital and Fiona Stanley Hospital Perth WA Australia.

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.

Keywords: burns; cytokines; flow cytometry; inflammation; lymphocytes; paediatrics.