Targeted multi-omic analysis of human skin tissue identifies alterations of conventional and unconventional T cells associated with burn injury

Elife. 2023 Feb 15:12:e82626. doi: 10.7554/eLife.82626.

Abstract

Burn injuries are a leading cause of unintentional injury, associated with a dysfunctional immune response and an increased risk of infections. Despite this, little is known about the role of T cells in human burn injury. In this study, we compared the activation and function of conventional T cells and unconventional T cell subsets in skin tissue from acute burn (within 7 days from initial injury), late phase burn (beyond 7 days from initial injury), and non-burn patients. We compared T cell functionality by a combination of flow cytometry and a multi-omic single-cell approach with targeted transcriptomics and protein expression. We found a significantly lower proportion of CD8+ T cells in burn skin compared to non-burn skin, with CD4+ T cells making up the bulk of the T cell population. Both conventional and unconventional burn tissue T cells show significantly higher IFN-γ and TNF-α levels after stimulation than non-burn skin T cells. In sorted T cells, clustering showed that burn tissue had significantly higher expression of homing receptors CCR7, S1PR1, and SELL compared to non-burn skin. In unconventional T cells, including mucosal-associated invariant T (MAIT) and γδ T cells, we see significantly higher expression of cytotoxic molecules GZMB, PRF1, and GZMK. Multi-omics analysis of conventional T cells suggests a shift from tissue-resident T cells in non-burn tissue to a circulating T cell phenotype in burn tissue. In conclusion, by examining skin tissue from burn patients, our results suggest that T cells in burn tissue have a pro-inflammatory rather than a homeostatic tissue-resident phenotype, and that unconventional T cells have a higher cytotoxic capacity. Our findings have the potential to inform the development of novel treatment strategies for burns.

Keywords: Conventional T cells; MAIT cells; Unconventional T cells; burn injury; human; immunology; inflammation; medicine; single-cell omics; skin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Burns* / metabolism
  • CD8-Positive T-Lymphocytes
  • Humans
  • Multiomics*
  • Skin / metabolism
  • T-Lymphocyte Subsets

Associated data

  • SRA/SRR23092707
  • SRA/SRR23092708