Gfi1 in innate immunity: a downstream effector of Toll like receptor signaling and a novel regulator of endotoxin tolerance

• Applicant: Professor Dr. Tarik Möröy
• Subject Area: Immunology
• Term: from 2002 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5356844

Gfi-1 is a 55kD nuclear zinc finger protein which until now has been considered to act solely as a T-cell specific transcriptional repressor. However, we have recently discovered that this protein is also expressed in granulocytes and LPS treated macrophages which implicated a role of this protein in the innate immune system. The phenotype of Gfi-1 deficient mice supported such a role since these animals die prematurely with symptoms similar to septic shock within 3 months of age. Moreover Gfi-1 null mice have a severe neutropenia and produce highly elevated levels of inflammatory cytokines as TNF and IL-10. Using combinatorial mutant mice we plan to determine how Gfi-1 modulates the systemic response to endotoxins or an infection with P. aeruginosa, which is one of the clinically most relevant opportunistic bacteria. In addition, we wish to explore the signal transduction pathways that are responsible for the activation of Gfi-1 expression in primary murine macrophages upon LPS treatment or P. aeruginosa infection. Finally, we aim to determine the effector genes and signaling pathways that are regulated by Gfi-1 in bacterially infected macrophages.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1110: Innate Immunity
• Participating Person: Professor Dr. Erich Gulbins