Here, Ting and colleagues provide an overview of the NLR gene family, detailing the initial discovery of NLRs and the key experiments that uncovered their biology. NLRs are well known for their roles as inflammasome receptors and regulators of inflammation but they also have less appreciated roles, for example, in embryogenesis and reproduction.

Clonal haematopoiesis — the occurrence of somatic mutations and mosaic chromosomal alterations in blood cells — is associated with age-related diseases, autoimmunity, immunodeficiency and haematological neoplasms. This Review describes how myeloid and lymphoid cell dysregulation underlies this association.

Macrophages are important for host immunity to infections and for clearing waste products from tissues, but they also maintain tissue health by regulating metabolism, neuronal functions and many other biological processes. Here, Elvira Mass and co-workers discuss the different tissue-specific macrophage populations that are found throughout the body, highlighting shared and unique aspects of their developmental trajectories, transcriptional programmes and physiological functions.

Koohy and co-workers discuss how we must turn to machine-learning approaches to define the antigen specificity of the many millions of possible T cell receptors. They review the models and methods currently being used to predict cognate antigens for orphan T cell receptors.