CARD–BCL-10–MALT1 signalling in protective and pathological immunity

CARD protein–BCL-10–MALT1 (CBM) signalosomes are multiprotein signalling platforms that control immune and inflammatory pathways in most tissues. After exposure to distinct immune triggers, these molecules form self-organizing filaments with MALT1 protease activity to regulate canonical nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways and the degradation of mRNA-binding proteins, which provides two layers of control of inflammatory gene expression. These CBM-regulated mechanisms are essential for host defence and tissue homeostasis, and numerous genetic alterations in CBM signalling components have been implicated in inherited and acquired immune-mediated diseases. This Review discusses the regulation and signalling of CBM complexes, their physiological roles and their pathophysiological functions in human immunodeficiency diseases, inflammatory disorders and cancers of the immune system. CARD protein–BCL-10–MALT1 (CBM) signalosomes are key regulators of innate and adaptive immunity and inflammation. This Review summarizes the regulation and function of CBM signalling for host defence and tissue homeostasis and the pathophysiological consequences of genetic CBM alterations in human disease.