SFB 854, Teilprojekt A23
The role of the atypical NF-κB inhibitory protein IκBNS in effector cells
The ubiquitously expressed transcription factor NF-κB is involved in a plethora of immunological processes and needs to be tightly regulated to fulfill these diverse functions. The regulation is ensured by typical and atypical inhibitory proteins. The so far only insufficiently characterized IκBNS belongs to the atypical NF-κB inhibitory protein which can activate as well as suppress NF-κB-mediated gene transcription. Most studies to elucidate the role of IκBNS in the regulation of immune responses were so far performed in defined in vitro or ex vivo settings, while the impact of IκBNS in controlling in vivo immune responses during systemic infections still remains largely unclear. We found that IκBNS-deficient mice in contrast to wild type animals are highly resistant to high-dose Listeria monocytogenes infection which is associated with broad alterations in the inflammatory program of innate immune cell subsets. As future prospect we will study the molecular mechanism underlying the IκBNS-dependent dysregulated signaling cascades and aim to identify molecular IκBNS targets involved in the severe outcome of infection. This would render IκBNS as specific therapeutic target for the treatment of infectious diseases driven by hyper-inflammatory immune responses.
Prof. Dr. Ingo Schmitz (SIME)