Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

Microfold cells (M-cell) are specialized cells of the intestine that sample luminal microbiota and dietary antigens. Here the authors show that epithelial non-canonical NFκB signalling, as induced by NIK, is important for M-cells maintenance, yet constitutive NIK activation is associated with gut inflammation and inflammatory bowel disease.

Regulatory T (Treg) cells are important for maintaining immune homeostasis by suppressing immune cell activation, but how the Treg cell pool is maintained is still unclear. Here the authors show that a kinase, Lkb1, operates in dendritic cells (DC) to inhibit Treg cell expansion and immunosuppression via mechanisms involving NF-kB/OX40L signalling.

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.

Nuclear factor-kappa B (NF-κB) signaling is regulated by ubiquitin to maintain immune homeostasis. Here the authors show that a peptidylprolyl isomerase, CYPJ, blocks TAB2/3 or LUBAC ubiquitin chain sensing and suppress NF-κB activation, with CYPJ-deficiency leading to susceptibility to inflammatory stimuli.