SP110 as a novel regulator of innate immune inflammasomes

The role of the human orthologue to Ipr1; SP110 is poorly understood  but polymorphic variants in the SP110 gene were identified as risk factors for disseminated and lymphoid manifestations of tuberculosis. Our recent findings that SP110 deficient cells show extraordinary inflammasome activity upon bacterial challenge is supported by the fact that both IL1β over activity and SP110 polymorphisms resulting in loss-of-function cause the same disease called hepatic veno-occlusive disease with immunodeficiency, indicating a relationship between SP110 and IL1β.

We hypothesize that SP110 is a central modulator of inflammasome activity and cell death; and necessary to harness the destructive capacity of detrimental inflammation initiated during certain pathogen challenge.

The project includes questions regarding

• The role of cell death for innate immune cell control of pathogens
• Inflammasome control and its effect on directing cellular death and how this interplays with inflammatory signaling
• The native role of SP110 (which to date is largely unknown we are in the process of deciphering this)