Dataset Information

Molecular imbalance mechanism of skin and blood leucocytes in severe burn patients at different burn times.

ABSTRACT:

Background

Severe burns are a leading cause of injuries worldwide and are usually accompanied by considerable morbidity and mortality. The purpose of this study was to investigate the changes of gene expression in blood and skin at different times after severe burn.

Methods

Firstly, the gene expression profiles of different burn time samples in GSE19743 and GSE8056 were analyzed. Secondly, the maladjusted gene network was identified by protein-protein interaction (PPI) network, and the genes in the network were enriched and analyzed. In addition, the key dysfunctional genes were identified by betweenness algorithm, and evaluated by survival analysis, Cox analysis, receiver operating characteristic (ROC) analysis. Finally, crosstalk analysis and enrichment analysis were carried out between the blood- and skin-specific differentially expressed genes (DEGs) at different burn times.

Results

The results showed that there were common DEGs in the blood and skin at different burn times. Importantly, we screened out the key dysfunctional genes BIRC5, NCAM1, PCNA, TOP2A, and VEGFA, which were related to the course of burns. Enrichment analysis showed that these maladjusted genes were mainly involved in the immune inflammation-related signal pathway. Additionally, significant crosstalk was identified between blood- and skin-specific genes at different burn times, especially in the blood. The signal pathways involved in specific genes represent their own pathological characteristics.

Conclusions

Both blood and skin tissues express common pathological changes and unique molecular mechanisms at different times after burn injury. The results of this study provide guidance for clinical personalized treatment.

SUBMITTER: Liang A

PROVIDER: S-EPMC9577754 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Molecular imbalance mechanism of skin and blood leucocytes in severe burn patients at different burn times.

Liang Anru A Qiu Fukui F Wu Fangxiao F Ruan Jiang J Zhu Lijuan L Rong Yongxian Y Li Junjun J

Annals of translational medicine 20220901 18

<h4>Background</h4>Severe burns are a leading cause of injuries worldwide and are usually accompanied by considerable morbidity and mortality. The purpose of this study was to investigate the changes of gene expression in blood and skin at different times after severe burn.<h4>Methods</h4>Firstly, the gene expression profiles of different burn time samples in GSE19743 and GSE8056 were analyzed. Secondly, the maladjusted gene network was identified by protein-protein interaction (PPI) network, an ...[more]

PMID: 36267773

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Project description:The importance and exact role of graft-resident leucocytes (also referred to as passenger leucocytes) in transplantation is controversial as these cells have been reported to either initiate or retard graft rejection. T cell activation to allografts is mediated via recognition of intact or processed donor MHC molecules on antigen-presenting cells (APC) as well as through interaction with donor-derived extracellular vesicles. Reduction of graft-resident leucocytes before transplantation is a well-known approach for prolonging organ survival without interfering with the recipient's immune system. As previously shown by our group, injecting mice with IL-2/anti-IL-2 complexes (IL-2cplx) to augment expansion of CD4 T regulatory cells (Tregs) induces tolerance towards islet allografts, and also to skin allografts when IL-2cplx treatment is supplemented with rapamycin and a short-term treatment of anti-IL-6. In this study, we investigated the mechanisms by which graft-resident leucocytes impact graft survival by studying the combined effects of IL-2cplx-mediated Treg expansion and passenger leucocyte depletion. For the latter, effective depletion of APC and T cells within the graft was induced by prior total body irradiation (TBI) of the graft donor. Surprisingly, substantial depletion of donor-derived leucocytes by TBI did not prolong graft survival in naïve mice, although it did result in augmented recipient leucocyte graft infiltration, presumably through irradiation-induced nonspecific inflammation. Notably, treatment with the IL-2cplx protocol prevented early inflammation of irradiated grafts, which correlated with an influx of Tregs into the grafts. This finding suggested there might be a synergistic effect of Treg expansion and graft-resident leucocyte depletion. In support of this idea, significant prolongation of skin graft survival was achieved if we combined graft-resident leucocyte depletion with the IL-2cplx protocol; this finding correlated along with a progressive shift in the composition of T cells subsets in the grafts towards a more tolerogenic environment. Donor-specific humoral responses remained unchanged, indicating minor importance of graft-resident leucocytes in anti-donor antibody development. These results demonstrate the importance of donor-derived leucocytes as well as Tregs in allograft survival, which might give rise to new clinical approaches.

Project description:Background: Paediatric burn patients, including those with non-severe burns, have an increased risk of admission to hospital for mental health conditions for many years after the burn, even in children too young at the time of the burn to remember the incident. This study aimed to investigate the long-term physiological impact of non-severe burn injuries and non-burn trauma (NBT) on the brain in mice to understand whether there is a sustained impact of such injuries on the brain that may be linked to the increased mental health morbidity observed in patients. Methods: Mice were exposed to either a non-severe burn injury, an excision injury of the same size (equivalent non-burn trauma), or a sham procedure. Behavioural tests were conducted at multiple timepoints to measure anxiety and depression-like behaviour. Mice were euthanised three months after the injury, and plasma and brain tissue, including the hippocampus and prefrontal cortex, were isolated and examined using RNA sequencing, mass spectrometry and nuclear magnetic resonance (NMR) to identify transcriptomic and metabolomic changes. Results: A significant change in behaviour was observed with an increase in sucrose consumption three months after injury in the burn group compared to sham. Significant changes in the transcriptome were identified in some brain regions at 3 months after burn trauma compared to the sham group. Differentially expressed genes associated with inflammatory and immune functions were identified in the burn group compared to controls. Significant changes were also observed in the lipid profile and tryptophan catabolites in the brain after burn trauma compared to sham. Conclusion: Sustained changes in the transcriptome and metabolome were identified in a mouse model of non-severe burns, supporting a likely sustained pro-inflammatory environment in the brain after this type of injury. The potential link between these changes and the poor long-term mental health outcomes observed in paediatric burn patients requires further investigation.

Dataset Information

Molecular imbalance mechanism of skin and blood leucocytes in severe burn patients at different burn times.

Background

Methods

Results

Conclusions

Publications

Molecular imbalance mechanism of skin and blood leucocytes in severe burn patients at different burn times.

Similar Datasets

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