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

• Published in: Clinical & translational immunology Vol. 13; no. 3; p. e1496
• Main Authors: Langley, Donna, Zimmermann, Kate, Krenske, Emma, Stefanutti, Giorgio, Kimble, Roy M, Holland, Andrew Ja, Fear, Mark W, Wood, Fiona M, Kenna, Tony, Cuttle, Leila
• Format: Journal Article
• Language: English
• Published: Australia John Wiley & Sons, Inc 01.01.2024; Wiley
• Subjects: Age; Biomarkers; Burn patients; Burns; CC chemokine receptors; Cell differentiation; Chemokines; Cytokines; Cytotoxicity; Dendritic cells; Effector cells; Flow cytometry; Gene expression; Helper cells; Homing behavior; Immune response; Infections; Inflammation; Injuries; Lasers; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Macrophages; paediatrics; Patients; Pediatrics; Peripheral blood mononuclear cells; Phenotypes; Respiratory tract infection; Scars; Tumor necrosis factor-α; Wound healing; paediatrics; cytokines; flow cytometry; lymphocytes; inflammation; burns
• ISSN: 2050-0068; 2050-0068
• DOI: 10.1002/cti2.1496

The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post-burn. 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. 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. 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.