Immunomodulatory extracellular vesicles arise after burn and polytraumatic injuries
Extracellular vesicles (EV) are rapidly emerging as novel mediators of immune dysfunction across several immune pathologies. We have described EV which arise after burn injury act as a key undiscovered reservoir for DAMPs, cytokines, and miRNA in humans and mice. These EV contained HMGB1/IL-1β complexes which induced increased transcription of cytokines IL-6 and IFNβ in human immune cells.
We extended this work to show that EVs can transfer hallmarks of immune dysfunction from burn to uninjured mice, and re-program human and mouse primary and transformed macrophages in vitro with similar functional outcomes and immune gene expression changes seen with their associated phase of post-burn immune dysfunction.
We investigated if EV cargo after burn injury can predict length of hospital stay. Unbiased LC-MS/MS proteomic analysis of early EVs (<72 h post-injury) from mice and humans showed some similarities including enrichment of acute phase response proteins such as CRP and SAA1. Semi-unbiased assessment of early human burn patient EVs found alterations consistent with increased proinflammatory signaling and loss of inhibition of CRP expression. In a sample of 50 patients with large burn injury, EV SAA1 and CRP were correlated with TBSA injury in both sexes and were correlated with length of hospital stay.
We are also examining the role of EV in other models of inflammation and have recently shown that EV purified from irradiation injury, chronic pancreatitis or sepsis patients contain a predictable miRNA cargo, and are working to correlate those identities with pathology of unresolved pancreatic inflammatory processes.

Selected References:
Seim RF, Willis ML, Wallet SM, Maile R*, Coleman LG*. Extracellular vesicles as regulators of immune function in traumatic injuries and sepsis. Shock: 2023 Shock. 2022 Dec 16. doi: 10.1097/SHK.0000000000002023. PMID: 36516458
Maile R, Willis ML, Herring LE, Prevatte A, Mahung C, Cairns BA, Wallet SM, Coleman LG Jr. Burn Injury Induces Proinflammatory Plasma Extracellular Vesicles That Associate with Length of Hospital Stay in Women: CRP and SAA1 as Potential Prognostic Indicators International Journal of Molecular Sciences 22(18):10083 2021 Sep; 22(18): 10083 DOI: 10.3390/ijms221810083