Human skin mucosal associated invariant T (MAID cells show increased pro-inflammatory cytokine expression following burn trauma

Abstract The role of T cells in burn trauma is an understudied research area explored primarily in mice, with sparse data in humans. Patients surviving an initial burn injury are at a high risk of infection, sepsis, and death. Unconventional T-cells such as mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that respond rapidly to pathogens. Circulating MAIT cells are primarily interferon (IFN)-gamma and tumor necrosis factor (TNF) producing when presented with a microbial-derived ligand on MHC class-1 related protein (MR1) or activated by cytokines interleukin (IL)-12 & IL-18. In this study, we obtained discarded burn (n=6) and normal (from discarded autograft, n=4) skin tissue from burn patients and compared unconventional T cell functionality by flow cytometry and single-cell RNA-sequencing (scRNA-seq). We did not find any significant differences between the frequency of total MAIT cells between burn injury or normal skin, 1.51 ± 1.42 and 2.98 ± 4.40, respectively. There is a significant higher level of CD38 expression in MAIT cells from burn injury tissue and a significant higher level of CD69 expression in MAIT cells from normal skin tissue. Skin MAIT cells in a burn injury show significantly higher levels of IFN-g and TNF before and after PMA-ionomycin stimulation compared to normal skin MAIT cells, which mainly produce IL-6 & IL-17A, suggesting that skin MAIT cells of burn patients show a MAIT cell phenotype that is more responsive to infection. We are characterizing these MAIT cell subtypes in further detail with scRNA-seq and anticipate presentation of that data at time of the conference. Our findings provide the means towards an understanding of the role that skin MAIT cells play in skin of patients with burn trauma.