Mechanisms and regulation of CD8 T cell-mediated autoimmune reactions against enteric neurons

• Applicant: Dr. Monica Sanchez Ruiz, since 4/2023
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456822245

Gastrointestinal dysmotility frequently manifests peri-/postinfectiously and chronic inflammatory bowel disease and may cause severe clinical symptoms. In patients with gastrointestinal dysmotility, we have identified a CD8 T cell-mediated inflammation of the enteric nervous system (ENS) followed by severe neuronal loss (75%). This observation raised the hypothesis of a CD8 T cell autoimmune response directed against enteric neurons. This hypothesis was verified in a preclinical mouse model in which ovalbumin was specifically expressed as autoantigen in enteric neurons. In this model, adoptively transferred ovalbumin-specific CD8 T cells fulminantly attacked and destroyed enteric neurons, clinically manifesting as gastrointestinal dysmotility. Interferon-gamma neutralization prevented lethal ileus. Here, we aim to precisely identifiy the interactions between enteric neurons and CD8 T cells as well as their regulation by antigens. Identification of pathogenetically relevant candidates and their functional targeting as well as the analysis of their expression in colonic biopsies obtained from patients with enteric ganglionitis will also yield innovative therapeutic approaches.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Professorin Dr. Martina Deckert, until 3/2023