Final Report Summary - CBM-INNATE (Regulation and Function of CARD9 / BCL10 / MALT1 Signalosomes in Innate Immunity and Inflammation)
This ERC Advanced Grant project investigated the molecular regulation and biological function of the CARD9/BCL10/MALT1 (CBM) signalosomes in the immune system. These signaling complexes are activated by distinct immune triggers and mediate the activation of canonical NF-κB transcription factors and MALT1 protease activity to control inflammatory gene expression and other immune pathways. These CBM-regulated mechanisms are critical for host defense and tissue homeostasis. Within this ERC project, molecular mechanisms of CBM activation in response to C-type lectin receptor signaling as well as nucleic acid sensors were identified. In addition, the specific function of the MALT1 protease in vivo has been revealed. Moreover, this project contributed to the discovery of human immuno-deficiency syndromes associated with genetic deficiencies within CBM components. Finally, using defined in vivo models, the project revealed physiological and pathophysiological functions of CBM signaling in intestinal immune homeostasis, colorectal cancer, as well as other inflammatory diseases.