T cells integrate signals from self-ligands not only during thymic development but also as they circulate through secondary lymphoid organs. These encounters with self in the periphery shape their activation and function, thereby ‘training’ T cells to interpret and respond to foreign antigens.

This Review compares the structure–function relationships of the apoptosome, inflammasomes and PIDDosome, which are the three main platforms activating the CARD-containing caspases caspase-9, caspase-1 and caspase-2, respectively. It highlights the consequences of genetic perturbations of these platforms and their therapeutic potential in humans.

This Review from Shokrollah Elahi considers how erythroid cells — including erythroid progenitors and precursors and mature red blood cells — can modulate immunity in different settings, including in infection, autoimmunity and cancer.

What is unique about the immune system of people who live to extreme old age? Here the authors describe that centenarians may achieve such longevity through several mechanisms, including limiting the pathological effects of inflammageing and immunosenescence, preservation of immune surveillance, sustained gut microbial diversity and maintenance of intestinal barrier integrity.