TY - JOUR TI - Targeted multi-omic analysis of human skin tissue identifies alterations of conventional and unconventional T cells associated with burn injury AU - Labuz, Daniel R AU - Lewis, Giavonni AU - Fleming, Irma D AU - Thompson, Callie M AU - Zhai, Yan AU - Firpo, Matthew A AU - Leung, Daniel T A2 - Kim, Brian S A2 - Zaidi, Mone A2 - de Andrade, Lucas F VL - 12 PY - 2023 DA - 2023/02/15 SP - e82626 C1 - eLife 2023;12:e82626 DO - 10.7554/eLife.82626 UR - https://doi.org/10.7554/eLife.82626 AB - 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. KW - burn injury KW - Unconventional T cells KW - skin KW - MAIT cells KW - Conventional T cells KW - single-cell omics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -