Dataset Information

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.

SUBMITTER: Langley D

PROVIDER: S-EPMC10921233 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

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

Langley Donna D Zimmermann Kate K Krenske Emma E Stefanutti Giorgio G Kimble Roy M RM Holland Andrew Ja AJ Fear Mark W MW Wood Fiona M FM Kenna Tony T Cuttle Leila L

Clinical & translational immunology 20240308 3

<h4>Objectives</h4>The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post-burn.<h4>Methods</h4>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 ...[more]

PMID: 38463658

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Project description:BackgroundTraumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24 h post-injury. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and naïve (control) brain tissue were used for microarray analysis. Ingenuity Pathway Analysis (IPA) software was used to identify molecular pathways and networks that were associated with the altered gene expression in brain tissues following TBI.ResultsInspection of the top fifteen biological functions in IPA associated with TBI in the ipsilateral tissues revealed that all had an inflammatory component. IPA analysis also indicated that inflammatory genes were altered on the contralateral side, but many of the genes were inversely expressed compared to the ipsilateral side. The contralateral gene expression pattern suggests a remote anti-inflammatory molecular response. We created a network of the inversely expressed common (i.e., same gene changed on both sides of the brain) inflammatory response (IR) genes and those IR genes included in pathways and networks identified by IPA that changed on only one side. We ranked the genes by the number of direct connections each had in the network, creating a gene interaction hierarchy (GIH). Two well characterized signaling pathways, toll-like receptor/NF-kappaB signaling and JAK/STAT signaling, were prominent in our GIH.ConclusionsBioinformatic analysis of microarray data following TBI identified key molecular pathways and networks associated with neural injury following TBI. The GIH created here provides a starting point for investigating therapeutic targets in a ranked order that is somewhat different than what has been presented previously. In addition to being a vehicle for identifying potential targets for post-TBI therapeutic strategies, our findings can also provide a context for evaluating the potential of therapeutic agents currently in development.

Dataset Information

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

Objectives

Methods

Results

Conclusion

Publications

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

Similar Datasets

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