Reviews & Analysis

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.

Activation of the unfolded protein response during immune cell activation has emerged as making an essential contribution to the response to infection and inflammation. In this Review, the authors discuss where, how and when a disbalanced unfolded protein response can become pathological and thus a potential therapeutic target.

A disseminated tumour cell will grow only if it arrives at a ‘fertile’ distant site, which as Ana Luísa Correia posits is determined largely by the immune context at the site. Site-specific differences in local immune cell types, ratios and spatial locations influence whether a disseminated tumour cell establishes metastases or is kept dormant.

In this Review, Marco Colonna provides a comprehensive summary of the triggering receptor expressed on myeloid cells (TREM) family of receptors. TREMs are important for modulating signalling in myeloid cells and have now been implicated in many different disease settings, including inflammatory diseases, autoimmunity, neurodegeneration  and cancer.

Neonatal Fc receptor (FcRn) supports host defence through its role in antibody recycling and transcytosis, as well as by regulating immune effector cells together with classical Fc receptors for IgG. However, in autoantibody-mediated disease, these activities can be harmful. FcRn-blocking strategies are now showing promise in the clinic.

In addition to their well-established role in haemostasis, platelets also have an active role in the immune response. Here the authors summarize the evidence linking platelet activation to immune dysregulation and organ damage in immune-mediated inflammatory diseases, and discuss the therapeutic potential of targeting platelets.

Galectins can modulate immune cells by binding to glycosylated proteins and lipids on the cell surface, or intracellularly via carbohydrate-dependent or carbohydrate-independent interactions. This Review explores the diverse ways in which galectins affect immunity and discusses the challenges in the field.

The authors propose a new grouping of glomerulonephritis disorders based on their underlying immunopathogenesis, with a view to improving diagnosis, mechanistic understanding and treatment of these immune-mediated kidney diseases.

This Review synthesizes our current mechanistic understanding of the cellular and molecular determinants of tissue-specific antifungal host defences derived from animal models of fungal disease, humans with fungal infection-manifesting inborn errors of immunity and patients treated with fungal infection-promoting, immune-targeted biologics.