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CBM-INNATE

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Regulation and Function of CARD9 BCL10 MALT1 Signalosomes in Innate Immunity...

Regulation and Function of CARD9 BCL10 MALT1 Signalosomes in Innate Immunity and Inflammation Acute inflammation is a response to infection or tissue damage that is critical for host protection and tissue homeostasis. However, deregulated or chronic inflammation is harmful to the host and can cause multiple diseases includ... ver más

31/01/2019

TUM-MED

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIV... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2019-01-31 No tenemos la información de la convocatoria

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TUM-MED

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Líder del proyecto

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIV... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Acute inflammation is a response to infection or tissue damage that is critical for host protection and tissue homeostasis. However, deregulated or chronic inflammation is harmful to the host and can cause multiple diseases including inflammatory bowel disease, rheumatoid arthritis, cardiovascular diseases, neuroinflammatory disease and cancer. Cells of the innate immune system sense microbial or sterile danger via pattern recognition receptors (PRRs). Subsequently, these PRRs engage intracellular signalling modules to elicit inflammatory effector mechanisms. We have recently identified the CARD9 / BCL10 / MALT1 (CBM) signalosome as a central proinflammatory signalling complex in innate immune cells. This molecular platform responds to stimuli from transmembrane SYK-coupled C-type lectin receptors and from intracellular danger sensors such as RIG-I-like helicases, NOD2 and presumably others to robustly activate NF-κB and MAPK pathways. Innate CBM signalling is engaged upon fungal, bacterial or viral recognition and upon sterile cell injury and it is essential for host protection in humans and mice. Still, it is unclear how the CARD9 / BCL10 / MALT1 signalosome is activated on a molecular level and how CBM responses are transduced to effector cascades. Moreover, although CARD9 polymorphisms are linked to various human inflammatory diseases, the cell type- and signal-specific roles of CBM signalosomes in complex diseases in vivo are unknown. Here we aim to take an integrated genetic, biochemical and in vivo approach to comprehensively dissect the regulation of the CARD9 / BCL10 / MALT1 complex in innate immunity and to define the role of this signalosome in clinically relevant inflammatory diseases. Mechanistic in vitro studies will be combined with the in vivo analysis of CBM function in genetically defined mouse models to gain better insights into the regulation of innate immunity and to pave the way to novel therapeutics for inflammatory diseases.

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