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 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.; Competing Interests: The authors have no conflicts of interest to declare. (© 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)