Analysis of inflammatory circuits during the Instant Blood-Mediated Inflammatory Reaction (A03)

• Subject Area: Endocrinology, Diabetology, Metabolism ; Immunology
• Term: from 2012 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213602983

The Instant Blood-Mediated Inflammatory Reaction (IBMIR) represents a major limitation after porcine islet xenotransplantation, as it leads to destruction of a substantial part of the islets transplanted in the liver. IBMIR is mediated by a complex interplay of multiple components of innate immunity. Our project focuses on understanding the inflammatory pathways regulating IBMIR with an emphasis on the recipient environment. In this context, we have recently identified novel breakthrough mechanisms involving innate immune memory. Innate immune memory has two opposed forms, trained innate immunity or innate immune tolerance, leading respectively to enhanced or reduced inflammation. Critical regulators of the balance between training and tolerance are changes of the metabolism of innate immune cells. Here, we will focus on metabolic mechanisms involved in innate immune cell activation and manipulate them towards innate immune tolerance in order to prevent IBMIR.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 127: Biology of Xenogeneic Cell and Organ Transplantation - From Bench to Bedside
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Heads: Professor Dr. Triantafyllos Chavakis; Professorin Dr. Barbara Ludwig, until 6/2016; Professorin Dr. Claudia Waskow, until 6/2016