MITOCHONDRIAL DAMAGE-ASSOCIATED MOLECULAR PATTERNS IMPACT LYMPHOCYTE FUNCTION AND CORRELATE WITH ORGAN HEALTH DURING NORMOTHERMIC MACHINE PERFUSION

Abstract

Damage-associated molecular pattern (DAMP) molecules from mitochondria (mitoDAMPs) are released following tissue injury. Innate immune cells promote inflammation in response to mitoDAMPs, yet how this is controlled and ultimately resolved is poorly understood. I demonstrate that mitoDAMPs contain arginase, which depletes L-arginine and induces an immunoregulatory program in lymphocytes. These data suggest that mitoDAMPs play a crucial role in regulating immune responses and offer insight into potential strategies for limiting inflammation and restoring tissue homeostasis following injury.

Elevated levels of mtDNA, a subset of mitoDAMPs, are associated with unfavorable clinical outcomes, and mtDNA is gaining recognition as a predictive biomarker for multiple disease processes. I demonstrate that mtDNA levels correlate with clinical parameters during normothermic machine perfusion (NMP). MtDNA is an inexpensive and rapidly measurable marker that can provide insight into liver function during NMP, potentially aiding evaluation of livers from extended criteria donors and improving efficiency of organ allocation.