Remote control of T cell exhaustion by muscle

• Applicant: Dr. Guoliang Cui
• Subject Area: Immunology ; Virology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429484112

Chronic viral infections and cancers frequently cause unwillingly loss of body weight and muscle atrophy, also known as cachexia. It remains incompletely understood if and how the reduction of muscle influence antiviral and anti-tumor immune cells (such as CD8+ T cell) metabolism, intracellular signaling and effector functions. Using mouse models with germ-line deficiency of IL-15 or muscle-specific ablation of IL-15, we observed that muscle-derived IL-15 play an essential role in antagonizing CD8+ T cell exhaustion. In this proposal, we will 1) investigate the underlying mechanisms through which IL-15 inhibits CD8+ T cell exhaustion 2) test if IL-15 administration protects against T cell exhaustion during chronic infection and 3) identify the signals inducing muscle production of IL-15. Our proposed work will highlight muscle as an important remote regulator of antiviral T cell exhaustion.

• DFG Programme: Research Grants